Magnetically controlled release of recombinant tissue plasminogen activator from chitosan nanocomposites for targeted thrombolysis

2016 ◽  
Vol 4 (15) ◽  
pp. 2578-2590 ◽  
Author(s):  
Jyh-Ping Chen ◽  
Chih-Hsin Liu ◽  
Hao-Lung Hsu ◽  
Tony Wu ◽  
Yu-Jen Lu ◽  
...  
Keyword(s):  
Controlled Release ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Targeted Delivery ◽  
Chitosan Nanoparticles ◽  
Recombinant Tissue Plasminogen Activator ◽  
Triggered Release ◽  
Magnetic Chitosan ◽  
Tissue Plasminogen ◽  
Thrombolysis Therapy

Targeted delivery and triggered release of rtPA-encapsulated magnetic chitosan nanoparticles with the guidance of a magnet could be used for remote-controlled thrombolysis therapy.

scholarly journals In acute ischemic stroke patients with smoking incidence, are more women than men more likely to be included or excluded from thrombolysis therapy?

2020 ◽  
Vol 16 ◽  
pp. 174550652092276
Author(s):  
Oluyemi R Rotimi ◽  
Iretioluwa F Ajani ◽  
Alexandria Penwell ◽  
Shyyon Lari ◽  
Brittany Walker ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Recombinant Tissue Plasminogen Activator ◽  
Stroke Patients ◽  
Initial Examination ◽  
Tissue Plasminogen ◽  
History Of ◽  
Thrombolysis Therapy

Background: Clinical factors associated with exclusion from recombinant tissue plasminogen activator in both men and women are not completely understood. The aim of this study is to determine whether there is a gender difference in clinical risk factors that excluded ischemic stroke patients with a history of smoking from recombinant tissue plasminogen activator. Methods: Retrospective data from a stroke registry were analyzed, and multivariable linear regression models were used to determine gender differences. Logistic regression models determined exclusion clinical risk factors for thrombolysis in male and female acute ischemic stroke patients with a history of smoking, while sequentially adjusting for sociodemographic, clinical, and stroke-related variables. The Kaplan–Meier survival analysis was used to determine the exclusion probabilities of men and women with a history of smoking within the stroke population. Results: Of the 1,446 acute ischemic stroke patients eligible for recombinant tissue plasminogen activator, 379 patients with a history of smoking were examined, of which 181 received recombinant tissue plasminogen activator while 198 were excluded from receiving recombinant tissue plasminogen activator. Of the 198 patients, 75 females and 123 males were excluded from receiving recombinant tissue plasminogen activator. After multivariable adjustment for age, National Institutes of Health scores, and stroke-related factors, females who present with weakness/paresis on initial examination (OR = 0.117, 95% CI, 0.025–0.548) and men who present with a history of previous transient ischemic attack (OR = 0.169, 95% CI, 0.044–0.655), antiplatelet medication use (OR = 0.456, 95% CI, 0.230–0.906), and weakness/paresis on initial examination (OR = 0.171, 95% CI, 0.056–0.521) were less likely to be excluded from recombinant tissue plasminogen activator (thrombolysis therapy). Conclusions: In an ischemic stroke population with a history of smoking, female smokers are more likely to be excluded from thrombolysis therapy in comparison to men, even after adjustment for confounding variables.

Investigation by HPLC of the Catabolism of Recombinant Tissue Plasminogen Activator in the Rat

1988 ◽  
Vol 60 (01) ◽  
pp. 107-112 ◽  
Author(s):  
Roy Harris ◽  
Louis Garcia Frade ◽  
Lesley J Creighton ◽  
Paul S Gascoine ◽  
Maher M Alexandroni ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Half Life ◽  
Recombinant Tissue Plasminogen Activator ◽  
Rat Plasma ◽  
High Molecular Weight Complex ◽  
Molecular Weights ◽  
Major Activity ◽  
Tissue Plasminogen

SummaryThe catabolism of recombinant tissue plasminogen activator (rt-PA) was investigated after injection of radiolabelled material into rats. Both Iodogen and Chloramine T iodination procedures yielded similar biological activity loss in the resultant labelled rt-PA and had half lives in the rat circulation of 1 and 3 min respectively. Complex formation of rt-PA was investigated by HPLC gel exclusion (TSK G3000 SW) fractionation of rat plasma samples taken 1-2 min after 125I-rt-PA injection. A series of radiolabelled complexes of varying molecular weights were found. However, 60% of the counts were associated with a single large molecular weight complex (350–500 kDa) which was undetectable by immunologically based assays (ELISA and BIA) and showed only low activity with a functional promoter-type t-PA assay. Two major activity peaks in the HPLC fractions were associated with Tree t-PA and a complex having a molecular weight of ̴ 180 kDa. HPLC fractionation to produce these three peaks at various timed intervals after injection of 125I-rt-PA showed each to have a similar initial rate half life in the rat circulation of 4-5 min. The function of these complexes as yet is unclear but since a high proportion of rt-PA is associated with a high molecular weight complex with a short half life in the rat, we suggest that the formation of this complex may be a mechanism by which t-PA activity is initially regulated and finally cleared from the rat circulation.

Bioavailability in Rats of Human Recombinant Tissue Plasminogen Activator After Subcutaneous and Intramuscular Injection

1986 ◽  
Vol 56 (03) ◽  
pp. 299-301 ◽  
Author(s):  
L J Garcia Frade ◽  
S Poole ◽  
S Hanley ◽  
L J Creighton ◽  
A D Curtis ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Inferior Vena ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Vena Cava ◽  
Recombinant Tissue Plasminogen Activator ◽  
Fibrin Plate ◽  
Tissue Plasminogen

SummaryThe bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.

Association of admission leukocyte count with clinical outcomes in acute ischemic stroke patients undergoing intravenous thrombolysis with recombinant tissue plasminogen activator

2020 ◽  
Vol 17 ◽  
Author(s):  
Jie Chen ◽  
Fu-Liang Zhang ◽  
Shan Lv ◽  
Hang Jin ◽  
Yun Luo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Leukocyte Count ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Functional Independence ◽  
Tissue Plasminogen ◽  
Poor Outcomes

Objective:: Increased leukocyte count are positively associated with poor outcomes and all-cause mortality in coronary heart disease, cancer, and ischemic stroke. The role of leukocyte count in acute ischemic stroke (AIS) remains important. We aimed to investigate the association between admission leukocyte count before thrombolysis with recombinant tissue plasminogen activator (rt-PA) and 3-month outcomes in AIS patients. Methods:: This retrospective study included consecutive AIS patients who received intravenous (IV) rt-PA within 4.5 h of symptom onset between January 2016 and December 2018. We assessed outcomes including short-term hemorrhagic transformation (HT), 3-month mortality, and functional independence (modified Rankin Scale [mRS] score of 0–2 or 0–1). Results:: Among 579 patients who received IV rt-PA, 77 (13.3%) exhibited HT at 24 h, 43 (7.4%) died within 3 months, and 211 (36.4%) exhibited functional independence (mRS score: 0–2). Multivariable logistic regression revealed admission leukocyte count as an independent predictor of good and excellent outcomes at 3 months. Each 1-point increase in admission leukocyte count increased the odds of poor outcomes at 3 months by 7.6% (mRS score: 3–6, odds ratio (OR): 1.076, 95% confidence interval (CI): 1.003–1.154, p=0.041) and 7.8% (mRS score: 2–6, OR: 1.078, 95% CI: 1.006–1.154, p=0.033). Multivariable regression analysis revealed no association between HT and 3-month mortality. Admission neutrophil and lymphocyte count were not associated with 3-month functional outcomes or 3-month mortality. Conclusion:: Lower admission leukocyte count independently predicts good and excellent outcomes at 3 months in AIS patients undergoing rt-PA treatment.

scholarly journals Intravenous thrombolysis for stroke in pregnancy should be administered if the benefit outweighs the risk: A case report and recommended diagnostic workup

2021 ◽  
Vol 17 ◽  
pp. 174550652199949
Author(s):  
Marek Bojda ◽  
Andrea Cimprichová ◽  
Bibiana Vavríková ◽  
Alena Filipková ◽  
Zuzana Gdovinová
Keyword(s):  
Case Report ◽  
Pregnant Woman ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Sudden Onset ◽  
Diagnostic Workup ◽  
Successful Outcome ◽  
Tissue Plasminogen

Introduction: There is an ongoing debate about the use of recombinant tissue plasminogen activator in acute stroke during pregnancy. The aim of our case report is to present that even in a small stroke centre intravenous thrombolysis can be used on a pregnant woman if the benefit outweighs the risk and to summarize the diagnostic workup in a pregnant woman with stroke. Case report: Our case describes a 31-year-old woman presenting in her third trimester with a sudden onset of slurred speech, severe right hemiparesis, facial nerve central palsy, eyes deviation to the left, right side hemianopia, hemisensory loss, psychomotor agitation and pain in the right lower limb. She was successfully treated with recombinant tissue plasminogen activator with almost complete recovery (NIHSS 1 after 10 days), and 23 days after intravenous thrombolysis, she delivered in the 37th week a healthy male infant. The first documented successful outcome from thrombolysis for this condition in Slovakia supports the notion of giving intravenous recombinant tissue plasminogen activator to pregnant patients with disabling ischaemic stroke who meet the criteria for thrombolysis. Discussion: At the end of case study, a recommended diagnostic workup for acute treatment of stroke in pregnant women is presented.

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