Academic literature on the topic 'Thrombolytic Agent'

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Journal articles on the topic "Thrombolytic Agent"

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Madonov, Pavel, Stanialav Leont’ev, Sergey Zotov, Maksim Ufimtsev, Svetlana Mishenina, and Dmitrii Kinsht. "Initial Results of Oral Thrombolytic Agent Clinical Application." Proceedings 2, no. 9 (July 20, 2018): 530. http://dx.doi.org/10.3390/proceedings2090530.

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At the moment, there is no oral thrombolytic drug on the world pharmaceutical market. The drug Trombovazim, which has a thrombolytic effect under oral administration, has been registered in Russia. It differs from all thrombolytics—it has a fundamentally different mechanism of action. It is not an activator of plasminogen. It independently dissolves a thrombus. It is a direct thrombolytic. The article presents the materials of the initial studies of the drug Trombovazim.
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Agnelli, G., MR Buchanan, F. Fernandez, J. Van Ryn, and J. Hirsh. "Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits." Blood 66, no. 2 (August 1, 1985): 399–401. http://dx.doi.org/10.1182/blood.v66.2.399.399.

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Abstract Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t- PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation.
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Agnelli, G., MR Buchanan, F. Fernandez, J. Van Ryn, and J. Hirsh. "Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits." Blood 66, no. 2 (August 1, 1985): 399–401. http://dx.doi.org/10.1182/blood.v66.2.399.bloodjournal662399.

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Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t- PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation.
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Qu, Shu, and Xingwei Ding. "Shear-, Sound-, and Light-Sensitive Nanoparticles for Thrombolytic Drug Delivery." Seminars in Thrombosis and Hemostasis 46, no. 05 (May 16, 2019): 587–91. http://dx.doi.org/10.1055/s-0039-1688490.

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AbstractThrombotic diseases, as potentially induced by blood clots or vascular embolization, frequently occur with high rates of mortalities worldwide. Current drug thrombolysis, a primary clinical therapy, may increase fatal risk of hemorrhage when thrombolysis agents become systemically distributed. Given current thrombolysis limitations, some novel drug delivery systems based on nanoparticles have been recently exploited to achieve a more controlled release of loaded thrombolytic agents, able to respond to environmental changes, and resulting in a safer thrombolysis. In this review, the authors outline and discuss some prominent examples of early and recent thrombolytic agent delivery systems using controlled release by physical stimuli (shear, sound and light). Shear-sensitive systems are designed to exploit the specific biomechanical feature of thrombosis, that is, the increased blood shear stress. Sound- and light-sensitive systems reflect “remote control” of drug release by responding to external ultrasound or light stimulus. These smart thrombolytic drug delivery systems hold promise for more effective and safer future thrombolytic therapy.
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Bizjak, Eric D., and Vincent F. Mauro. "Thrombolytic Therapy: A Review of Its Use in Acute Myocardial Infarction." Annals of Pharmacotherapy 32, no. 7-8 (July 1998): 769–84. http://dx.doi.org/10.1345/aph.17350.

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OBJECTIVE: To review the literature on the use of thrombolytic agents in the pharmacotherapeutic management of acute myocardial infarction (AMI). DATA SOURCE: English-language clinical trials, reviews, and editorials derived from MEDLINE (January 1966–September 1997) and/or cross-referencing of selected articles. STUDY SELECTION: Articles that were selected best represent the clinical trials researching the role for thrombolytics in the therapy of AMI to improve morbidity and mortality. DATA SYNTHESIS: AMI is one of the leading causes of mortality in the US. Following supportive data that the most common cause of an AMI is an intracoronary thrombus, clinical investigation has demonstrated that intravenous thrombolytic agents improve survival rates in patients who experience an AMI. Several clinical trials have been conducted to determine whether one thrombolytic agent is superior to others with respect to improving mortality. At present, only the first Global Use of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial has reported any statistically significant difference in mortality rate. In this trial, “front-loaded” alteplase induced a statistically significant (p < 0.001) 1% absolute reduction in 30-day and 1-year mortality compared with streptokinase. This has led to alteplase being the preferred thrombolytic at many US institutions. However, the results of GUSTO-I have been questioned by some on the basis of either study design or clinical significance. CONCLUSIONS: Thrombolytic agents have secured a place in the treatment of AMI due to their well-proven reduction in mortality rates. In general, comparative trials have demonstrated minimal differences in efficacy among these agents. Probably just as important as choosing which thrombolytic agent to use is ensuring that a patient experiencing an AMI is administered thrombolytic therapy unless a contraindication to receive such therapy exists in the patient and/or the patient is a candidate to receive an emergent intracoronary procedure. Trials also indicate that the sooner thrombolytics can be administered, the greater the benefit to the patient.
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Nikitin, Dmitri, Seungbum Choi, Jan Mican, Martin Toul, Wi-Sun Ryu, Jiri Damborsky, Robert Mikulik, and Dong-Eog Kim. "Development and Testing of Thrombolytics in Stroke." Journal of Stroke 23, no. 1 (January 31, 2021): 12–36. http://dx.doi.org/10.5853/jos.2020.03349.

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Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited efficacy and notable hemorrhagic complication rates, leaving room for improvement. A comprehensive understanding of basic and clinical research pipelines as well as the current status of thrombolytic therapy will help facilitate the development of new thrombolytics. Compared with alteplase, an ideal thrombolytic agent is expected to provide faster reperfusion in more patients; prevent re-occlusions; have higher fibrin specificity for selective activation of clot-bound plasminogen to decrease bleeding complications; be retained in the blood for a longer time to minimize dosage and allow administration as a single bolus; be more resistant to inhibitors; and be less antigenic for repetitive usage. Here, we review the currently available thrombolytics, strategies for the development of new clot-dissolving substances, and the assessment of thrombolytic efficacies <i>in vitro</i> and <i>in vivo</i>.
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Verhaeghe, Raymond. "Thrombolysis in Arterial Occlusion." Thrombosis and Haemostasis 82, S 01 (1999): 109–11. http://dx.doi.org/10.1055/s-0037-1615565.

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SummaryIntra-arterial thrombolytic therapy has replaced systemic intravenous infusion of thrombolytic agents as a treatment modality for arterial occlusion in the limbs. Several catheter-guided techniques and various infusion methods and schemes have been developed. At present there is no scientific proof of definite superiority of any agent in terms of efficacy or safety but clinical practice favours the use of urokinase or alteplase. Studies which compared thrombolysis to surgical intervention suggest that thrombolytic therapy is an appropriate initial management in patients with acute occlusion of a native leg artery or a bypass graft. Underlying causative lesions are treated in a second step by endovascular or open surgical techniques. Severe bleeding is the most feared complication: the risk of hemorrhagic stroke is 1-2%.
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Ringleb, Peter, Robert Stingele, and Werner Hacke. "Thrombolysis in Acute Cerebrovascular Disease: Indications and Limitations." Thrombosis and Haemostasis 82, no. 08 (1999): 983–86. http://dx.doi.org/10.1055/s-0037-1615942.

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IntroductionLarge-scale trials have shown that thrombolytic therapy reduces mortality and preserves left ventricular function in patients with acute myocardial infarction (AMI). As most ischemic strokes are thromboembolic in origin,1 there appears to be a rationale for the use of thrombolytic agents in the management of ischemic stroke.Thrombolytic agents differ in their mechanisms of action, but in general, they act by promoting the conversion of plasminogen into plasmin, resulting in fibrin degradation and clot dissolution. Streptokinase and recombinant tissue plasminogen activator (rt-PA) are the agents that have been the most widely investigated in stroke studies. Ancrod, the active agent in the venom of the Malayan pit viper, is primarily considered an anticoagulant, although it does stimulate endogenous t-PA release from the vascular endothelium and may enhance local thrombolysis. Urokinase is used in local, intra-arterial thrombolysis but has not been subjected to large clinical trials since computed tomography (CT) diagnosis became widely available.
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Perkins, W. R., D. E. Vaughan, S. R. Plavin, W. L. Daley, J. Rauch, L. Lee, and A. S. Janoff. "Streptokinase Entrapment in Interdigitation-Fusion Liposomes Improves Thrombolysis in an Experimental Rabbit Model." Thrombosis and Haemostasis 77, no. 06 (1997): 1174–78. http://dx.doi.org/10.1055/s-0038-1656133.

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SummaryThe successful design of new thrombolytic agents depends on providing these agents with increased clot selectivity. As recently demonstrated (10), entrapment of tissue plasminogen activator into liposomes apparently provided the selective targeting needed to improve the efficacy of this fibrinolytic agent. To test whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent with a different mode of action and inactivation, we compared liposomal streptokinase with free streptokinase in an experimental rabbit model of thrombolysis.First we adapted a new method to produce liposomes of high entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the encapsulation of streptokinase. This system was then tested in an in vivo rabbit model of thrombolysis where animals with established clots were infused with either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase, free streptokinase + empty liposomes, or the corresponding amount of empty liposomes or saline. Significant differences (p <0.05) in the percent clot lysis were observed between saline control (22.4 ± 3.3%; mean ± S.E.), free streptokinase (36.3 ± 3.4%), and liposomal streptokinase (47.4 ± 1.4%). Importantly, animals treated with empty liposomes experienced a level of thrombolysis (32.4 ± 2.8%) not different to that produced by free streptokinase or empty liposomes plus free streptokinase (38.0 ± 2.0%). We believe the effect of liposomes alone is due to a transient redistribution or margination of circulating platelets.When tested in rabbits immunized against streptokinase, liposomal (33.8 ± 1.5%) but not free streptokinase (29.3 ± 2.1%) showed significant thrombolytic activity compared to saline (22.4 ± 3.3%) (p <0.05). The thrombolytic activity was comparable to free streptokinase in nonimmunized rabbits. This suggests liposomal streptokinase would have better thrombolytic activity than streptokinase alone and still provide to those patients possessing high levels of anti-streptokinase antibodies (5% of the population) the equivalent degree of therapy expected from free streptokinase.
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Kim, Dongjune, Susan M. Shea, and David N. Ku. "Lysis of arterial thrombi by perfusion of N,N’-Diacetyl-L-cystine (DiNAC)." PLOS ONE 16, no. 2 (February 25, 2021): e0247496. http://dx.doi.org/10.1371/journal.pone.0247496.

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The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The agents and adjuncts tested were tPA, ADAMTS-13, abciximab, N-acetyl cysteine, and N,N’-Diacetyl-L-cystine (DiNAC). Most of the agents, including tPA, had little thrombolytic effect on the white clots. In contrast, perfusion of DiNAC lysed thrombi as quickly as 1.5 min, which ranged up to 30 min at lower concentrations, and resulted in an average reduction in surface area of 71 ± 20%. The clot burden was significantly reduced compared to both tPA and a saline control (p<0.0001). We also tested the efficacy of all agents on red fibrinous clots formed in stagnant conditions. DiNAC did not lyse red clots, whereas tPA significantly lysed red clot over 48 h (p<0.01). These results lead to a novel use for DiNAC as a possible thrombolytic agent against acute arterial occlusions that could mitigate the risk of hyper-fibrinolytic bleeding.
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Dissertations / Theses on the topic "Thrombolytic Agent"

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Björklund, Erik. "Early risk stratification, treatment and outcome in ST-elevation myocardial infarction /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6050.

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Gruber, Matthew J. "Ultraharmonic and Broadband Cavitation Thresholds for Ultrasound Contrast Agents in an In-Vitro Flow Model." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1428066108.

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Yu, Xinge. "Stroke Study: Novel Animal Models and Innovative Treatment Strategy." Ohio University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1450735023.

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Farret, Neto Abdo. "Utiliza??o intraco?gulo de espuma fibrinol?tica - prepara??o, caracteriza??o e atividade in vitro de uma espuma de estreptoquinase e proposta de uma nova abordagem terap?utica." Universidade Federal do Rio Grande do Norte, 2014. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13868.

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Made available in DSpace on 2014-12-17T14:25:23Z (GMT). No. of bitstreams: 1 AbdoFN_TESE.pdf: 1739510 bytes, checksum: 7f520b9c4a32fd74e279d017c0bdd143 (MD5) Previous issue date: 2014-03-31
Foam was developed as a novel vehicle for streptokinase with the purpose of increasing the contact time and area between the fibrinolytic and the target thrombus, which would lead to a greater therapeutic efficacy at lower doses, decreasing the drug s potential to cause bleeding. Fibrinolytic foams were prepared using CO2 and human albumin (at different v:v ratios), as the gas and liquid phases, respectively, and streptokinase at a low total dose (100,000 IU) was used as fibrinolytic agent conveyed in 1 mL of foam and in isotonic saline solution. The foams were characterized as foam stability and apparent viscosity. The thrombolytic effect of the streptokinase foam was determined in vitro as thrombus lysis and the results were compared to those of a fibrinolytic solution (prepared using the same dose of streptokinase) and foam without the fibrinolytic. In vitro tests were conducted using fresh clots were weighed and placed in test tubes kept at 37 ? C. All the samples were injected intrathrombus using a multiperforated catheter. The results showed that both foam stability and apparent viscosity increased with the increase in the CO2:albumin solution ratio and therefore, the ratio of 3:1 was used for the incorporation of streptokinase. The results of thrombus lysis showed that the streptokinase foam presented the highest thrombolytic activity (44.78 ? 9.97%) when compared to those of the streptokinase solution (32.07 ? 3.41%) and the foam without the drug (19.2 ? 7.19%). We conclude that fibrinolytic foam showed statistically significant results regarding the enhancement of the lytic activity of streptokinase compared to the effect of the prepared saline solution, thus it can be a promising alternative in the treatment of thrombosis. However, in vivo studies are needed in order to corroborate the results obtained in vitro
Uma espuma foi desenvolvida como novo ve?culo para a estreptoquinase com vistas a aumentar a ?rea de contato e o tempo de perman?ncia junto ao trombo, de modo a se obter maior efici?ncia terap?utica em doses menores, diminuindo suas potenciais complica??es hemorr?gicas. A espuma fibrinol?tica foi preparada com CO2, albumina humana e estreptoquinase, em dispositivo desenvolvido para tal fim, com diferentes raz?es de fases g?s/l?quido. Ensaios de estabilidade e viscosidade aparente foram realizados para caracteriza??o das espumas e a escolha da mais est?vel. A estreptoquinase em dose total reduzida (100.000 UI) foi utilizada como fibrinol?tico veiculado em 1 mL de espuma e em solu??o salina isot?nica (0,9%). A espuma sem fibrinol?tico tamb?m foi utilizada como comparativo. Testes in vitro foram realizados utilizando-se co?gulos frescos, que foram pesados e colocados em tubos de ensaio mantidos a 37?C. As espumas com e sem fibrinol?tico e a solu??o fibrinol?tica foram testadas por aplica??o intraco?gulo em doses id?nticas atrav?s de cateter multiperfurado e pistola de inje??o. Os resultados in vitro evidenciaram atrav?s da diminui??o dos pesos dos co?gulos, que a espuma trombol?tica apresentou atividade l?tica de 44,78 ? 9,97%, enquanto as mesmas doses da estreptoquinase em solu??o salina isot?nica promoveram 32,07 ?3,41% de lise dos co?gulos. Na espuma sem fibrinol?tico a redu??o do trombo foi de 19,2 ? 7,19%. Conclui-se que a espuma fibrinol?tica apresentou resultados estatisticamente significativos no tocante ? potencializa??o da atividade l?tica da estreptoquinase, quando comparado ao efeito da solu??o preparada com solu??o salina, podendo ser uma alternativa promissora nos tratamentos das tromboses. Os dados obtidos sinalizam para necessidade de estudos in vivo para comprova??o dos obtidos nos in vitro
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Evaristo, Eli Faria. "Tratamento trombolítico intravenoso no acidente vascular cerebral isquêmico: experiência da clínica neurológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-27042007-131655/.

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O uso intravenoso do ativador tecidual do plasminogênio está aprovado para o tratamento do acidente vascular cerebral isquêmico há alguns anos e estão publicadas diretrizes e recomendações para o seu uso. O atendimento hospitalar precisa ser organizado a fim de tornar esse tratamento exeqüível e seguro, alcançando os resultados esperados. O objetivo deste estudo foi verificar a exeqüibilidade e a segurança do tratamento trombolítico intravenoso nos pacientes tratados pela Clínica Neurológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, assim como avaliar as características desses pacientes, sua evolução clínica, as complicações do tratamento e os preditores prognósticos. Também foi avaliado o desempenho do atendimento hospitalar, através da análise do tempo das diversas etapas do atendimento, em quatro diferentes grupos de pacientes com base no local do primeiro atendimento médico. Foram tratados 51 pacientes entre Junho de 1998 e Agosto de 2005, primeiramente atendidos no Pronto Socorro de Neurologia (22 pacientes), Instituto do Coração (22 pacientes) e enfermarias do Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (3 pacientes), assim como no Hospital Universitário (4 pacientes). Os tempos do atendimento, representados por suas respectivas medianas, foram: entre o ictus e a admissão (55 minutos); entre a admissão e a análise da tomografia computadorizada de crânio (35 minutos); entre a admissão e o início do tratamento trombolítico (90 minutos) e entre o ictus e o início do tratamento trombolítico (160 minutos). De uma maneira geral, o desempenho do atendimento melhorou durante o período do estudo. Entretanto, a análise comparativa dos grupos revelou que os tempos entre a admissão e a análise da tomografia computadorizada de crânio e entre a admissão e o início do tratamento trombolítico foram maiores no Instituto do Coração (p = 0,002 e p = 0,01, respectivamente) do que no Pronto Socorro de Neurologia e Hospital Universitário. O principal mecanismo causador do acidente vascular cerebral isquêmico foi embolia de origem cardíaca (54%). A maioria dos pacientes tratados chegou ao hospital com déficits neurológicos graves (mediana 17 na Escala de AVC do NIH). Resultado funcional excelente em 3 meses, definido como pontuações 0 ou 1 na Escala de Rankin modificada, foi observado em 29% dos casos e hemorragia cerebral sintomática em 6% dos casos. Em conclusão, o tratamento trombolítico intravenoso com ativador tecidual do plasminogênio no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foi exeqüível e seguro. A intensidade do déficit neurológico na admissão, mensurada pela Escala de AVC do NIH e a redução igual ou maior que quatro pontos nesta escala em 24 horas foram preditores prognósticos independentes.
Intravenous use of tissue plasminogen activator has been approved for acute ischemic stroke treatment for some years and guidelines and recommendations about its use have been published. Hospital attendance needs to be organized in order to become this treatment feasible and safe, reaching the expected results. The objective of this study was verify feasibility and safety of intravenous thrombolytic therapy in patients who were treated at Neurology Department of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo as well evaluating characteristics of these patients, their clinical outcome, complications of therapy and outcome predictors. Hospital attendance performance was also evaluated through time analysis of several steps of attendance in four different patient groups based on the place of the first medical attendance. Fifty one patients were treated between June 1998 and August 2005, primarily attended at Neurology Emergency Department (22 patients), Heart Institute (22 patients) and wards of Central Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (3 patients) as well at University Hospital (4 patients). Attendance times, represented by its median were: between symptoms onset and hospital admission (55 minutes); between hospital admission and computed cranial tomography analysis (35 minutes); between hospital admission and thrombolytic therapy onset (90 minutes) and between symptoms onset and thrombolytic therapy onset (160 minutes). As a general rule, hospital attendance performance improved during study period. However, comparative analysis of groups disclosed that time between hospital admission and computed cranial tomography analysis as well time between hospital admission and thrombolytic therapy onset were longer at Heart Institute (p = 0,002 and p = 0,01, respectively) than at Neurology Emergency Department and University Hospital. The main acute ischemic stroke mechanism was cardiac emboli (54%). Most of treated patients arrived at hospital with serious neurologic impairment (NIH Stroke Scale median 17). Excellent functional outcome in 3 months, defined as scoring 0 or 1 by modified Rankin Scale was observed in 29% and symptomatic cerebral hemorrhage in 6% of the cases. In conclusion, intravenous thrombolytic therapy with tissue plasminogen activator at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo was feasible and safe. The intensity of the neurological impairment at hospital admission, as measured by NIH Stroke Scale, and four-point or more score reduction on this scale at 24 hours were independent outcome predictors.
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SMITH, DENISE ANNE BUSH. "In vitro Characterization of Echogenic Liposomes (ELIP) for Ultrasonic Delivery of Recombinant Tissue-type Plasminogen Activator (rt-PA)." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1214234148.

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Books on the topic "Thrombolytic Agent"

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Kotb, Essam. Fibrinolytic bacterial enzymes with thrombolytic activity. Heidelberg: Springer, 2012.

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A, Mousa Shaker, ed. Anticoagulants, antiplatelets, and thrombolytics. Totowa, N.J: Humana Press, 2004.

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Anticoagulants, antiplatelets, and thrombolytics. 2nd ed. New York, NY: Humana, 2010.

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1927-, Sasahara Arthur A., and Loscalzo Joseph, eds. New therapeutic agents in thrombosis and thrombolysis. 2nd ed. New York: M. Dekker, 2003.

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Taylor, George Jesse. Thrombolytic therapy for acute myocardial infarction. Boston: Blackwell Scientific Publications, 1992.

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J, Del Zoppo Gregory, Mori Etsuro 1951-, and Hacke W. 1948-, eds. Thrombolytic therapy in acute ischemic stroke II. Berlin: Springer-Verlag, 1993.

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C, Becker Richard, ed. The modern era of coronary thrombolysis. Boston: Kluwer Academic Publishers, 1994.

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Morganroth, Joel, and E. Neil Moore, eds. Risk/Benefit Analysis for the Use and Approval of Thrombolytic, Antiarrhythmic, and Hypolipidemic Agents. Boston, MA: Springer US, 1989. http://dx.doi.org/10.1007/978-1-4613-1605-3.

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Joel, Morganroth, and Moore E. Neil, eds. Risk/benefit analysis for the use and approval of thrombolytic, antiarrhythmic, and hypolipidemic agents: Proceedings of the Ninth Annual Symposium on New Drugs & Devices, October 27 & 28, 1988. Boston: Kluwer Academic Publishers, 1989.

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Antithrombotic drug therapy in cardiovascular disease. Dordrecht: Springer, 2010.

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Book chapters on the topic "Thrombolytic Agent"

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Rafeeq, Hamza, Muhammad Anjum Zia, Asim Hussain, Ayesha Safdar, Muhammad Bilal, and Hafiz M. N. Iqbal. "Role of Streptokinase as a Thrombolytic Agent for Medical Applications." In Industrial Applications of Microbial Enzymes, 271–93. Boca Raton: CRC Press, 2022. http://dx.doi.org/10.1201/9781003202998-14.

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Agersborg, H. P. K., and J. Latts. "Is It Practical to Develop a Class III Antiarrhythmic Agent?" In Risk/Benefit Analysis for the Use and Approval of Thrombolytic, Antiarrhythmic, and Hypolipidemic Agents, 157–66. Boston, MA: Springer US, 1989. http://dx.doi.org/10.1007/978-1-4613-1605-3_11.

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Ostermann, H., and U. Schmitz-Huebner. "Thrombolytic agents." In Electrocardiography and Cardiac Drug Therapy, 332–51. Dordrecht: Springer Netherlands, 1989. http://dx.doi.org/10.1007/978-94-009-1081-2_24.

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Verstraete, M. "The Hunt for the Ideal Thrombolytic Agent: Mutants of tPA and uPA, Chimera of Both Molecules, Fibrolase." In Handbook of Experimental Pharmacology, 493–520. Berlin, Heidelberg: Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-642-56637-0_19.

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Zeymer, Uwe, and Karl-Ludwig Neuhaus. "New Thrombolytic Agents." In Contemporary Cardiology, 243–65. Totowa, NJ: Humana Press, 1999. http://dx.doi.org/10.1007/978-1-59259-731-4_10.

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Collen, D., and H. R. Lijnen. "New Generation Thrombolytic Agents." In Developments in Cardiovascular Medicine, 15–26. Boston, MA: Springer US, 1994. http://dx.doi.org/10.1007/978-1-4615-2618-6_2.

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Matsuo, O. "New Thrombolytic Agents: Basic Development." In Thrombolytic Therapy in Acute Ischemic Stroke III, 182–87. Tokyo: Springer Japan, 1995. http://dx.doi.org/10.1007/978-4-431-68459-6_21.

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Adgey, A. A. J., and J. A. Purvis. "Bolus Administration of Thrombolytic Agents." In Update in Intensive Care and Emergency Medicine, 27–33. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-84423-2_4.

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Verstraete, M. "Perspectives on Newer Thrombolytic Agents." In Limitation of Infarct Size, 147–55. Berlin, Heidelberg: Springer Berlin Heidelberg, 1989. http://dx.doi.org/10.1007/978-3-642-73585-1_17.

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Summaria, Louis. "The Biochemistry of Thrombolytic Agents." In Acute Coronary Care, 61–66. Boston, MA: Springer US, 1985. http://dx.doi.org/10.1007/978-1-4613-3828-4_7.

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Conference papers on the topic "Thrombolytic Agent"

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Loscalzo, J. "THE EFFICACY AND RELATIVE FIBRIN SELECTIVITY OF PROUROKINASE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643573.

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The use of thrombolytic agents in acute myocardial infarction has gained widespread acceptance as an important early therapeutic option. Acute coronary thrombosis has been found in approximately 80% of patients with acute infarction and the use of standard thrombolytic agents opens these occluded vessels in most cases. Unfortunately, in many individuals standard agents also produce a systemic lytic state with its attendant hemorrhagic complications. Prourokinase (PUK) has been shown to be a relatively fibrin selective thrombolytic agent in vitro owing to its localized conversion to urokinase at the clot surface. Because of this desirable property, we studied the efficacy and selectivity of PUK in vivo in 19 patients with acute myocardial infarction. Each of these patients was documented by angiography to have a totally occluded infarct-related artery. Each patient was treated within six hours (range: 2 to 5.8 hours) of the onset of symptoms with 62.5 mg of PUK derived from the human kidney cell line, TCL598, infused intravenously over 90 minutes. Complete vessel patency was achieved in nine patients within 61 ± 19 minutes of the start of the infusion without apparent hemorrhagic complications. We evaluated the effect of PUK on fibrinogen, on nonspecific fibrinogen degradation products (FDP) the the fibrinogen/fibrin I peptide, Bβ 1-42, as well as on the specific fibrin degradation products, D-dimer (XDP) and the fibrin II peptide, Bβ 15-42. Values for these parameters measured before and at the end of the 90-minute infusion of PUK are given as the mean ± S.E.M.We conclude that PUK is an effective agent with which to achieve coronary thrombolysis and that at the doses used in this study, it aDDears to be relatively fibrin selective.
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Bossaert, L., H. Demey, L. Colemont, and H. HRM. "PREHOSPITAL THROMBOLYTIC TREATMENT: A FEASIBILITY STUDY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642982.

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Aim of the study: Thrombolysis is the treatment of choice in acute myocardial infarction (AMI). The delay between onset of symptoms and administration of thrombolytic drugs is critical for successful reperfusion and myocardial salvage. We studied the feasibility and safety of early prehospital thrombolytic treatment of AMI “at home”Methods: Eminase(R)(APSAC;BRL 26921 ) was used as thrombolytic agent: its long half-life allows administration as a single IV bolus. The study was performed in collaboration with a well organised group of GP's, extensively retrained in ECG and CPR for the purpose of this study. Whenever a GP made the tentative diagnosis of AMI of less than 2 hours, inclusion and exclusion criteria were reviewed using a check-list, and the mobile intervention team of the hospital (MITUZA), consisting of CCU physicians and emergency nurses, was activated. After rechecking all criteria, including a 12 lead ECG, brief medical history and physical examination, a single IV bolus of 30 U Eminase(R) was given, followed by transferral to the CCU. Follow-up included estimation of infarct-size and LV function using biochemical, ECG, radionuclide and angiographic methods.Results: Up till now, 15 male patients (age=57±9) have been treated using this protocol. Initial prehospital treatment consisted of Eminase(R) IV in 10 (reperfusion 9/10). Subsequent in-hospital treatment was streptokinase in 3 (reperfusion 2/3). In the 11 reperfused patients, PTCA was performed in 7 and CABG in 4. After onset of symptoms, the GP arrived after 55±24 min (15-90 min), Eminase(R) was administered after 95±28 min (75-130 min). The total calculated time gain (interval between treatment at home and admission in the CCU) was 42±15 min (20-75 min). There were no adverse events.Conclusion: This pilot study indicates that prehospital thrombolytic treatment of AMI is feasible and safe, resulting in a considerable time gain. Early reperfusion was obtained in 90%. Collaboration with a well organised and trained group of GP's, clearly defined inclusion and exclusion criteria and administration of the thrombolytic drug exclusively by experienced critical care physicians are mandatory.
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Del Zoppo, G. J., S. M. Otis, J. Zyroff, W. Hacke, H. Zeumer, and L. A. Harker. "INTRA-ARTERIAL THROMBOLYTIC THERAPY IN ACUTE MIDDLE CEREBRAL ARTERY STROKE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643891.

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18 patients presenting with acute carotid territory stroke, secondary to angiographically demonstrated occlusion of the middle cerebral artery (MCA), have been treated within 8 hours of the onset of acute symptoms by local intra-arterial infusion of urokinase or streptokinase. All patients were screened by baseline CT cerebral scan to exclude intracerebral hemorrhage as a cause of the acute stroke. 14 patients demonstrated complete, 2 partial, and 2 no recanalization (reopening) of the previously occluded artery following a 1 to 2 hour infusion of the fibrinolytic agent.10 of the 14 patients displaying complete recanalization had complete neurological recovery or improvement with residual neurological deficits, while the 2 patients who did not display recanalization did not improve clinically. No clinical improvement was observed in the absence of recanalization.Hemorrhagic transformation of cerebral ischemic areas may be classified as hemorrhagic infarction (minimal hemorrhage, no clinical deterioraton) and parenchymatous hemorrhage (mass effect, clinical deterioration). Minor infarction-related hemorrhages without detectable neurological sequelae (hemorrhagic infarctions) were found by CT scan in 4 patients; all displayed complete recanalization; and all hemorrhagic infarctions resolved.This uncontrolled prospective clinical experience suggests that early local infusion of thrombolytic agents in selected patients may be efficacious and safe.
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Takada, Y., Y. Sugawara, Y. Makino, and A. Takada. "KINETIC ANALYSES OF THE ACTIVATION OF GLU- OR LYS-PLASMINOGEN BY STREPTOKINASE IN THE PRESENCE OF FIBRIN OR ITS DEGRADATION PRODUCTS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644419.

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Human plasminogen was activated better by streptokinase (SK) in the presence of fibrin or its degradation products(potentiating agents). Such potentiating agents must be mixed with SK and plasminogen simultaneously. The addition of potentiating agents to the mixture of SK and plasminogen did not result in any enhancement of the activator activity of SK-plasminogen complex. Since potentiating agents such as fibrin bind to lysine binding sites (LBS) of plasminogen, and SK was known to bind to light chain side of plasminogen, it appears that a trimolecular complex of SK, plasminogen and a potentiating agent is a better enzyme than a complex of SK and plasminogen. The effectiveness of the potentiation was in the order of fibrin> SK-potentiator(early FgDP)> fibrinogen >fragment D >fragment E, when Glu-plasminogen was activated by SK. When Lys-plasminogen was used, fragment E was more effective than fragment D, thus in the order of fibrin> SK potentiator> fibrinogen>fragment E >fragment D. Such enhancement of the activation of plasminogen by fibrin or potentiating agents is more significant in the presence of lower concentration of SK. Increase in the concentration of SK did not result in much enhancement of the activation of plasminogen. Kinetic analyses indicated that kcat of the trimolecular complex (SK, plasminogen and potentiating agent) was higher than SK-plasminogen complex, without change in Km. These results suggest that a trimolecular complex of SK, plasminogen and potentiating agent converts plasminogen to plasmin more effectively than a dimole-cular complex of SK and plasminogen. Considering the fact that the plasma concentrations of thrombolytic agents such as SK or UK were low even after drip infusion of their large dose Intravenously, the potentiation of the activation of plasminogen by SK in the presence of fibrin maybe significant in the mechanisms of thrombolytic therapy.
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Pilger, E. J., J. Lammer, H. Bertuch, and H. Steiner. "INTRAARTERIAL THROMBOLYSIS BY STREPTOKINASE-GLU-PLASMINOGEN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643002.

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In order to predict usefulness of streptokinase (SK), urokinase (UK) and streptokinase-glutamin-plasminogen (SK-Glu-Plg) for intraarterial fibrinolysis, an in vitro test was designed. Fibrin plates with and without plasminogen were incubated with SK, UK and SK-Glu-Plg (in molar ratios of 1:1, 2:1 and 1:2). On the fibrin plates containing plasminogen the highest fibrinolytic activity was observed with UK; on the fibrin plates without plasminogen, SK-Glu-Plg in a molar ratio of 1:2 was superior. We concluded, that plasmin would be synthesized by SK and Glu-Plg. In order to examine the in vivo efficacy of these different fibrinolytic agents, 120 patients suffering from peripheral artery occlusion were randomized into three treatment groups for local thrombolysis. The technique of Hess and coworkers was used for local thrombolytic therapy. In group I local fibrinolysis was performed with SK (2500 IU/5 min), in group II UK (4000 IU/5 min) was used and in group III the lytic agent consisted of SK-Glu-Plg (2500 IU/5 min). The primary recanalization rate was equal in all groups: 86%, 89% and 83% in group I, II and III respectively. However the duration required for the procedure and thus the total amount of fibrinolytic agent used was significantly different (p < 0,001) between the three groups: 2,3 ± 1,4; 2,1 ± 1,2 and 1,1 ±0,8 hours for groups I,II and III, respectively (mean ± SEM) . We conclude that SK-Glu-Plg or plasmin itself has the highest efficacy as a fibrinolytic agent for intraarterial thrombolysis. Since the intra-thrombotic concentration of Pig is unknown in an individual patient an empirically chosen dose of SK of UK may either be to high or to low for optimal thrombolysis.
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Quertermous, T., J. M. Schnee, M. S. Runge, G. R. Matsueda, N. W. Hudson, J. G. Seidman, and E. Haber. "EXPRESSION OF A RECOMBINANT ANTIBODY-TARGETED THROMBOLYTIC MOLECULE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644616.

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We have recently shown that targeting tissue-type plasminogen activator (t-PA) by covalent linkage to a fibrin-specific monoclonal antibody (59D8) produces a more potent thrombolytic agent which also induces less fibrinogenolysis. A recombinant molecule encoding a t-PA-59D8 fusion protein was constructed to provide a ready source of this agent for further study, and to allow tailoring of the active moities for maximal activity. DNA sequence coding for the 59D8 heavy chain (HC) antigen combining site was cloned from a lambdaphage library by selection with a joining region probe. Gene segments coding for this cloned HC rearrangement, the amino portion of the mouse gamma 2b HC constant region, and the catalytic B chain of t-PA were joined in the pSV2-gpt expression vector. The desired coding sequence was confirmed by nucleotide sequence analysis. The construct was transfected by electroporation into 59D8 hybridoma HC loss variants. Transfectants were screened for antifibrin antibody activity. Positive clones were shown to produce mRNA which hybridized to the human t-PA gene in Northern blot analysis. Supernatants from 5 of these clones were subjected to affinity chromatography on a synthetic fibrin-like peptide-Sepharose column followed by a benzamidine-Sepharose column. Western blots of SDS polyacrylamide gels run under reducing conditions revealed binding to a 60 kd band by a monoclonal antihuman t-PA antibody, consistent with a 59D8 HC-t-PA fusion protein. Also, binding to a 25 kd band by goat anti-mouse Fab indicated the presence of 59D8 light chain. Affinity purified protein was shown to have amidolytic activity of similar potency to t-PA in a chromogenic substrate assay utilizing S-2288. Bifunctionality of the purified protein was demonstrated first by an assay which requires the protein to bind to immobilized fibrin and simultaneously exhibit activity in the S2288 assay, and second by simultaneous fibrin and iodinated anti-t-PA binding.
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Vogel, G., and M. Machulik. "THROMBOLYTIC EFFECTS OF A POLYANIONIC COMPOUND (PENTOSAN POLYSULPHATE SP54 ) IN GERIATRIC PATIENTS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643038.

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In geriatric patients the use ofstreptokinase or urokinase is oftenlimited by contraindications, particularly hypertension. As it has been demonstrated by different authors, the polyanionic compound pentosanpolysulphate SP 54 induced an activation of both intrinsic and extrinsic pathway of fibrinolysis and produced a mild decrease of blood prssure. From thise characteristics pentosan polysulphate SP54 should be anideal thrombolytic agent in geriatric patients. To clarify this, an open prospective studie was performed. 24 patient(16 females, 8 males ) age 65 -78 years , suffering from thromboembolicprocesses ( 8 deep vein thrombosis(DVT), 16 thrombosis of reti na vessels ( TRV) were included. Pentosan polysulphat SP 54 (BENE-PHARMA Munchen, F.R.G.) was administred byintravenous infusion 300 mg daily over a period of 10 days. Venographyor ophthalmoskopie were repeated atday 11.Results:Side effects: Bleeding 0 ; thrombocytopenia 2It is concluded from these results, that pentosan polysulphate SP54is an useful thrombolytic agent in particular in geriatric patients suffering from hypertension.
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Mukhametova, L., R. Aisina, K. Gerchkovich, and E. Ivanova. "Reducing the Side Effects of Thrombolytic Agent by Regulating its Release Rate from Microcapsules." In 63rd Annual Meeting of the Society of Thrombosis and Haemostasis Research. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1680193.

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Stassen, J. M., and D. Collen. "ON THE MECHANISM OF THE IN VIVO SYNERGISM BETWEEN TISSUE-TYPE PLASMINOGEN ACTIVATOR (t-PA) AND SINGLE CHAIN UROKINASE-TYPE PLASMINOGEN ACTIVATOR (scu-PA)." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643793.

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t-PA and scu-PA, in molar ratios between 1:4 and 4:1 do not act synergically in vitro (Thromb. Haemost. 56,35,1986) but display marked synergism in a rabbit model (Circulation 74, 838, 1986) and in man (Am. Heart J. 112, 1083, 1986). To investigate the mechanism of in vivo synergism in the rabbit model (J. Clin. Invest. 71, 368, 1983), t-PA and scu-PA were infused 1) simultaneously over 4 hrs, 2) t-PA over 1 hr, then 15 min later scu-PA over 2 hrs and 3) scu-PA over 1 hr, then 15 min later t-PA over 2 hrs.Significant synergism on thrombolysis is observed when t-PA and scu-PA are infused simultaneously or when t-PA is followed by scu-PA but not when scu-PA is followed by t-PA. These results suggest that low dose t-PA induces some plasminogen activation, sufficient to partially degrade fibrin, exposing COOH-terminal lysines with high affinity for plasminogen (Eur. J. Biochem. 140, 513, 1984). scu-PA might then activate surface-bound Glu-pla-minogen more efficiently.Sequential therapy with t-PA (or any other agent which "predigests" the thrombus), followed by scu-PA might constitute an alternative to simultaneous infusion of synergistic thrombolytic agents.
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Haigwood, N., E.-P. Pâques, G. Mullenbach, G. Moore, L. DesJardin, and A. Tabrizi. "IMPROVEMENT OF T-PA PROPERTIES BY MEANS OF SITE DIRECTED MUTAGENESIS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643841.

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The clinical relevance of tissue-plasminogen-activator (t-PA) as a potent thrombolytic agent has recently been established. It has however been recognized that t-PA does not fulfill all conditions required for an ideal thrombolytic pharmaceutical agent; for example, its physiological stability and its short half life in vivo necessitate the use of very large clinical doses. We have therefore attempted to develop novel mutant t-PA proteins with improved properties by creating mutants by site-directed mutagenesis in M13 bacteriophage. Seventeen mutants were designed, cloned, and expressed in CHO cells. Modifications were of three types: alterations to glycosylation sites, truncations of the N- or C-termini, and amino acids changes at the cleavage site utilized to generate the two chain form of t-PA. The mutant proteins were analyzed in vitro for specific activity, fibrin dependence of the plasminogen activation, fibrin affinity, and susceptibility to inhibition by PAI.In brief, the results are: 1) some unglycosylated and partially glycosylated molecules obtained by mutagenesis are characterized by several-fold higher specific activity than wild type t-PA; 2) truncation at the C-terminus by three amino acids yields a molecule with increased fibrin specificity; 3) mutations at the cleavage site lead zo a decreased inhibition by PAI; and 4) recombinants of these genes have been constructed and the proteins were shown to possess multiple improved properties. The use of site directed mutagenesis has proved to be a powerful instrument to modulate the biological properties of t-PA.
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