scholarly journals Effect Of Topical DLBS 1425 On Tissue Plasminogen Activator (tPA) Expression In Trabecular Meshwork Of Wistar Rats

2021 ◽  
Vol 8 (1) ◽  
pp. 15-20
Author(s):  
Utami Widijanto ◽  
Trilaksana Nugroho ◽  
Maharani Cahyono

Introduction: Tissue plasminogen activator (tPA) in the trabecular meshwork (TM) is a serine protease that important to maintain the aquos outflow resistance by activating the matrix metalloproteinase (MMP). It can cause a degradation of the extracellular matrix, which can maintain the normal flow of aquos humor. However, the use of anti-inflammatory drugs has been shown to reduce the expression of tPA, leading to an increase in the outflow resistance. Therefore, we propose the use of DLBS 1425, an extract of Phaleria macrocarpa which has been proven to have anti-inflammatory effects. Aim : This study aims to determine the expression of tPA in Wistar rats’ TM. Methods : An experimental laboratory study with  post-test only randomized controlled group design was performed. Twenty-two Wistar rats were divided into two groups, the control and the experimental. The experimental group was given topical DLBS 1425 at a dose of 6 times / day, for 4 weeks. The control group was given drops of Hyalub Minidose® 6 times / day, for 4 weeks. tPA expression on TM was examined by immunohistochemical staining. Data were collected and processed using the SPSS 15.0 for Windows. Results : The mean tPA expression in TM with Allred scores in the experimental group (0.18 ± 0.60) was significantly lower (p <0.001) than the control group (6.27 ± 0.91). Conclusion : Topical DLBS 1425 suppresses the expression of tPA on the trabecular meshwork of Wistar rats. Key words: tissue plasminogen activator, trabecular meshwork, DLBS 1425, Phaleria macrocarpa.

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72447 ◽  
Author(s):  
Sandeep Kumar ◽  
Shaily Shah ◽  
Hai Michael Tang ◽  
Matthew Smith ◽  
Teresa Borrás ◽  
...  

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jeffrey Leya ◽  
Elisabeth Donahey ◽  
Megan Rech

Introduction: Early treatment of acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset is associated with neurologic improvement. A risk of rtPA is hemorrhagic conversion, which has a higher incidence in patients with elevated blood pressure at presentation. Current literature supports the use of blood pressure goals (<185/110 mm Hg) in patients qualifying for rtPA, but the effects of anti-hypertensive (anti-HTN) medications within the first 24 hours of AIS on outcomes has not been evaluated. Hypothesis: AIS patients requiring anti-HTN medications (anti-HTN group) before rtPA have a poorer outcome at 90 days compared to those that do not need anti-HTN medications (control group). Methods: This was a retrospective cohort study of patients >18 years diagnosed with AIS from January 2011 through December 2015 who received one or multiple anti-HTN medication(s) prior to rtPA administration, compared to control patients who did not. Primary endpoint was poor outcome at 90 days, defined as a modified Rankin Scale (mRS) of ≥3. Univariate analysis with Chi-square, Fisher’s exact test or t-test was performed. Multivariate analysis was conducted. Results: Of 235 patients evaluated for AIS, 145 (61.7%) were included. Baseline demographics were well matched, though more patients in the anti-HTN group had a history of HTN (86.7% vs. 62.5%, p<0.01), diabetes (33.3% vs. 17.5%, p=0.04) and chronic kidney disease (20% vs. 7.5%, p=0.04). There was no difference in the primary endpoint of poor outcome (mRS ≥3) between groups who received blood pressure medication versus those who did not (37% anti-HTN group vs. 30% control, p=.374). There was no difference in hemorrhagic conversion (13.3% anti-HTN group vs. 6.3% control, p=.187). Mortality at 90 days did not differ between groups (11% who received anti-HTN vs. 7.5%, p=.508). Conclusion: No difference was observed in poor outcomes, hemorrhagic conversion, or 90-day mortality in patients receiving anti-HTN medications prior to rtPA compared to those that did not. These results suggest that aggressive blood pressure management should be used to control hypertension in AIS who may qualify for rtPA, though larger, randomized trials are needed to confirm this finding.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Eyad Almallouhi ◽  
Sami Al kasab ◽  
Ali Alawieh ◽  
Reda M Chalhoub ◽  
Mohammad Anadani ◽  
...  

Introduction: Intra-arterial tissue plasminogen activator (IA-tPA) can be used as rescue therapy during mechanical thrombectomy for stroke patients, mostly in the setting of distal occlusion. The outcomes of IA-tPA has not been assessed in large-scale multi-center studies yet. Methods: We used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which included prospectively maintained databases of 11 thrombectomy-capable stroke centers in the US, Europe, and Asia. We compared the baseline characteristics, procedural metrics, rate of symptomatic intracranial hemorrhage (sICH), and long-term functional outcomes between thrombectomy patients who received rescue IA-tPA and a control group of thrombectomy patients with matched age, National Institute of Health stroke scale (NIHSS) on presentation, location of occlusion and IV-tPA receipt. Results: A total of 2827 thrombectomy patients were included in the STAR registry. Out of those, 205 patients received IA-tPA. We matched 191 patients from the IA-tPA group with a control group of 191 patients (table 1). No difference was seen in age, sex, race, vascular risk factors, or Alberta Stroke Program Early CT (ASPECT) score between both groups. In addition, procedural metrics, including onset to groin time, the procedure duration, and rate of successful recanalization (modified Thrombolysis in Cerebral Infarction score≥2b) were similar. Finally, similar outcomes were noted in both groups, including the rate of sICH and good 90-day functional outcome (modified Rankin scale≤2). Conclusion: The use of IA-tPA as an adjunctive treatment to mechanical thrombectomy was safe but did not result in a higher rate of successful recanalization or good long-term functional outcomes.


Author(s):  
И.Г. Попова ◽  
С.Б. Назаров ◽  
О.Г. Ситникова ◽  
Г.Н. Кузьменко ◽  
М.М. Клычева ◽  
...  

Введение. Новорожденные, родившиеся у матерей с патологией во время беременности, составляют группу высокого риска тромботических и геморрагических осложнений, которые повышаются при наличии у новорожденных перинатальной патологии. Цель исследования: оценить показатели, характеризующие состояние системы фибринолиза и сосудистой стенки в крови новорожденных, родившихся у матерей с преэклампсией (ПЭ), для прогнозирования риска тромботических и геморрагических осложнений у таких детей. Материалы и методы. Обследовано 60 новорожденных, родившихся у матерей с ПЭ. Контрольную группу составили 30 новорожденных от матерей без ПЭ. Исследовали венозную кровь, взятую у новорожденных на 3–5-е сутки жизни. В крови определяли уровень тканевого активатора плазминогена (t-РА), ингибитора тканевого активатора плазминогена (PAI-1) и тромбомодулина. Результаты. Выявлено, что у новорожденных от матерей с ПЭ на 3–5-е сутки жизни отмечаются признаки повреждения эндотелия и повышение фибринолитической активности крови, на что указывает повышение содержания t-РА, PAI-1 и тромбомодулина в крови. Заключение. Полученные данные свидетельствуют о риске развития геморрагических осложнений у таких детей. Background. Neonates born to mothers with pathology during pregnancy are at high risk of thrombotic and hemorrhagic complications that are increased if neonates have perinatal pathology. Objectives: to assess blood parameters characterizing fibrinolysis and vascular wall of neonates born to mothers with preeclampsia (РЕ), to predict the risk of hemorrhagic complications in these children. Patients/Methods. 60 neonates born to mothers with РЕ were examined. The control group consisted of 30 neonates born to mothers without РЕ. We studied levels of tissue plasminogen activator (t-PA), inhibitor of tissue plasminogen activator (PAI-1) and thrombomodulin (TM) in venous blood taken from neonates on the 3–5th days of life. Results. In neonates born to mothers with PE we revealed on the 3–5th days of life increased blood levels of t-PA, PAI-1 and TM that characterized endothelial damage and increased blood fibrinolytic activity. Conclusions. The data obtained indicate the risk of hemorrhagic complications development in these children.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Tao Peng ◽  
George L Britton ◽  
Jaroslaw Aronowski ◽  
Davide Cattano ◽  
Melvin E Klegerman ◽  
...  

BACKGROUND: Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. Intravenous (iv) tissue plasminogen activator (tPA) in combination with the neuroprotective gas, xenon (Xe), is a promising strategy for ischemic stroke treatment. However, Xe delivery by inhalation may reduce oxygen uptake and tPA activity. We have developed novel Xe-containing echogenic liposomes (Xe-ELIP). In this study, we investigated the therapeutic effect of Xe-ELIP in a rat embolic stroke model. METHODS: Xe-ELIP was prepared by the pressurized-freeze method. Thrombotic strokes were induced in male Sprague-Dawley rats (n=16) by injecting a 13mm long blood clot into the middle cerebral artery (MCA). In the treatment group, tPA (10mg/kg) was infused intravenously at 2 hours after the onset occlusion. Xe-ELIP was administrated into the common carotid artery just before iv tPA. Continuous wave ultrasound (1 MHz, 50% duty cycle, 0.5 W/cm 2 ) was applied to trigger Xe release from ELIP during the 5 min of Xe-ELIP administration. Behavioral tests (limb placement, grid walking and beam walking) were conducted three days after the thrombotic stroke. Two mm-thick coronal brain sections were cut and stained with TTC to determine infarct size. RESULTS: The thrombotic stroke control group without any treatment exhibited the largest damage and infarct size (17±5% of the whole brain); tPA treatment reduced the damage and the infarct size to 5.2±0.4% of (p=0.025 vs stroke). tPA treatment in combination with Xe-ELIP further reduced the infarct size to 1.5±0.4% (p=0.05 vs tPA group) ( Fig 1a, 1b). Behavioral deficit correlated with the infarct volume reduction. Regional blood flow velocity monitored by a laser Doppler flow meter was the same in both tPA and tPA+Xe-ELIP treatment groups. CONCLUSIONS: This study has demonstrated a significant neuroprotective effect of ELIP-encapsulated xenon released by application of 1 MHz ultrasound. Xe-ELIP can be used in combination with tPA without affecting tPA thrombolytic activity.


1981 ◽  
Author(s):  
C Korninger ◽  
O Matsuo ◽  
R Suy ◽  
J M Stassen ◽  
D Collen

Experimental thrombosis was produced in an isolated 4 cm section of the femoral vein in the groin region of beagle dogs using a mixture of 125I-labeled human fibrinogen (6 × 106 cpm), dog blood, thromboplastin and thrombin. Saline, 1,000,000 IU of urokinase or 100,000 Units (1 mg) of highly purified tissue plasminogen activator (isolated from the culture fluid of human melanoma cells) was infused intravenously over four hours. The extent of thrombolysis was calculated from the difference between the radioactivity introduced in the clot and that in the recovered clot six hours after the start of the infusion.In four control animals thrombolysis was 31.0 ± 3.0% (mean ± S.D.). Infusion of urokinase in 3 dogs resulted in 42.7 ± 14.3% lysis. In 5 dogs receiving plasminogen activator thrombolysis was 65.6 ± 21.6%. During infusion the blood radioactivity rose significantly (from 2.5 to 6.6% of the total) in the tissue plasminogen activator group; only a slight rise was observed in the urokinase group and a progressive decline in the control group.Neither in the controls nor in the tissue plasminogen activator treated animals significant activation of plasminogen, consumption of α-antiplasmin or fibrinogen breakdown occurred and no major bleeding was noted. Infusion of urokinase, however, resulted in systemic activation of the fibrinolytic system with extensive fibrinogen breakdown causing a significant bleeding tendency.It is concluded that in the experimental model used human tissue plasminogen activator has higher specific thrombolytic and a lower systemic fibrinogenolytic effect than urokinase.


2021 ◽  
Author(s):  
FATMA BURCU BELEN APAK ◽  
Gulbahar Yuce ◽  
Deniz Ilhan Topcu ◽  
Ayse Gultekingil ◽  
Yunus Emre Felek ◽  
...  

Abstract Background: A substantial group of patients suffer coagulopathy of Covid-19 (CAC) and are presented with thrombosis. The pathogenesis involved in CAC is not fully understood.Objectives: We evaluated the hemostatic and inflammatory parameters of 51 hospitalized Covid-19 adult patients and 21 controls. The parameters analyzed were danger signal molecule (High molecular weight group box protein-1/HMGBP-1), platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, endothelial protein C receptor (EPCR), soluble E-selectin, soluble P-selectin, thrombomodulin, tissue plasminogen activator (TPA), plasminogen activator inhibitor-1 (PAI-1), soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), β-thromboglobulin, antithrombin and protein C. The main objective of our study was to investigate which part of the hemostatic system was mostly affected at the admission of Covid-19 patients and whether these parameters could differentiate intensive care unit (ICU) and non-ICU patients. Patients and Methods:In this prospective case-control study, 51 patients ≥18 years who are hospitalized with the diagnosis of Covid-19 and 21 healthy control subjects were included. We divided the patients into two groups according to their medical progress, either into ICU and non-ICU group. Regarding the outcome, patients were again categorized as survivor and non-survivor groups. Blood samples were collected from patients at admission at the time of hospitalization before administration of any treatment for Covid-19. The analyzes of the study were made with the IBM SPSS V22 program. p < 0.05 was considered statistically significant.Results:A total of 51 adult patients (F/M: 24/27) (13 ICU and 38 non-ICU) were included in the study cohort. The mean age of the patients was 68.1 ± 14.4 years. The control group consisted of 21 age and sex-matched healthy individuals. All of the patients were hospitalized, in a group of 13 patients, Covid-19 progressed to severe form and were hospitalized at ICU. We found out that the levels of fibrinogen, prothrombin time (PT), endothelial protein-C receptor (EPCR), D-dimer, soluble E-selectin, soluble P-selectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) were increased; whereas, the levels of soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), antithrombin and protein-C were decreased in Covid-19 patients compared to the control group at hospital admission. Tissue plasminogen activator was the only marker that had a significantly different median level between ICU and non-ICU groups (p<0.001).Conclusions:In accordance with the previous literature, we showed that Covid-19 associated coagulopathy is distinct from sepsis-induced DIC with prominent early endothelial involvement and fibrinolytic shut-down. Reconstruction of endothelial function at early stages of infection may protect patients to progress to ICU hospitalization. We believe that after considering the patient’s bleeding risk, early administration of LMWH therapy at Covid-19 even in at outpatient setting may be useful both for restoring endothelial function and anticoagulation. The intensity of anticoagulation in non-ICU and ICU Covid-19 patients should be clarified with further studies.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Urai Kummarg ◽  
Siriorn Sindhu ◽  
Sombat Muengtaweepongsa

Background. Intravenous recombinant tissue plasminogen activator (i.v. rt-PA) is the milestone treatment for patients with acute ischemic stroke. Stroke Fast Track (SFT) facilitates time reduction, guarantees safety, and promotes good clinical outcomes in i.v. rt-PA treatment. Nursing case management is a healthcare service providing clinical benefits in many specific diseases. The knowledge about the efficacy of a nurse case management for Stroke Fast Track is limited. We aim to study the effect of nurse case management on clinical outcomes in patients with acute ischemic stroke involving intravenous recombinant tissue plasminogen activator (i.v. rt-PA) treatment. Methods. Seventy-six patients with acute ischemic stroke who received i.v. rt-PA treatment under Stroke Fast Track protocol of Thammasat University Hospital were randomized into two groups. One group was assigned to get standard care (control) while another group was assigned to get standard care under a nurse case management. The National Institute of Health Stroke Scale (NIHSS) at 24 hours after treatment between the control and the experimental groups was evaluated. Results. Time from triage to treatment in the experimental group was significantly faster than in the control group (mean = 39.02 and 59.37 minutes, respectively; p=.001). The NIHSS at 24 hours after treatment in the nurse case management group was significantly improved as compared to the control group (p=.001). No symptomatic intracranial hemorrhage (sICH) was detected at 24 hours after onset in both groups. Conclusion. The nurse case management should provide some benefits in the acute stroke system. Although the early benefit is demonstrated in our study, further studies are needed to ensure the long-term benefit and confirm its profit in patients with acute ischemic stroke.


2019 ◽  
pp. 112067211989162
Author(s):  
Jan Janusz Sniatecki ◽  
Gregory Ho-Yen ◽  
Benjamin Clarke ◽  
Ramez Barbara ◽  
Stephen Lash ◽  
...  

Purpose: To evaluate visual and anatomic outcomes following pars plana vitrectomy and intravitreal or subretinal tissue plasminogen activator for submacular hemorrhage in patients with age-related macular degeneration. Methods: This was a retrospective study on patients with a minimum follow-up of 12 months undertaken at a tertiary referral center. Data collected include demographic details, visual and optical coherence tomography changes, surgical details, and complications. Surgical results were compared with patients who were age and lesion size matched and treated with anti-vascular endothelial growth factor injections alone. Results: There were 36 patients in surgical and 18 patients in control group. Patients in surgical arm had pars plana vitrectomy, intravitreal tissue plasminogen activator with air 24 (67%), 6 (16%) with C3F8 gas, 1 (3%) with SF6 gas, 4 (11%) subretinal tissue plasminogen activator with air, and 1 (3%) with C2F6 as post-operative tamponade. Mean LogMAR in tissue plasminogen activator group at baseline was 1.56, and it was improved at all time points 1.06 at 1 month (p < 0.05), 0.91 at 6 months (p < 0.05), and 1.07 at 1 year (p < 0.05). Mean best corrected visual acuity in control group at baseline was 1.22LogMAR with no significant improvement at any time points: 1 month (1.27), 6 months (1.35), and 12 months (1.36). Complications included retinal detachment 5%, vitreous hemorrhage 7.5%, and cataract 19%. Conclusion: Pars plana vitrectomy with intravitreal (or subretinal) tissue plasminogen activator and pneumatic displacement can offer better outcome in comparison to anti-vascular endothelial growth factor alone in patients with submacular hemorrhage secondary to age-related macular degeneration.


Sign in / Sign up

Export Citation Format

Share Document