In Vitro Studies on Degradation of Gamma-L-Glutamyl-L-Cysteine and Gamma-L-Glutamyl-D-Cysteine in Blood: Implications for Treatment of Stroke

Treatment for ischemic stroke involves a thrombolytic agent to re-establish blood flow in the brain. However, delayed reperfusion may cause injury to brain capillaries. Previous studies indicate that the antioxidant gamma-L-glutamyl-L-cysteine (γ-Glu-Cys) contributes to reducing reperfusion injury to the cerebral vasculature in rats, when administered intravascularly. To determine the stability of γ-Glu-Cys in blood, the peptide was incubated in rat serum in vitro, and its degradation was quantified by high-pressure liquid chromatography. The half-time (t1/2) for degradation of γ-Glu-Cys was 11 ± 1 minute (mean ± SD, n = 3). A similar pattern of degradation was observed when γ-Glu-Cys was incubated in the presence of human plasma (t1/2 = 17 ± 8 minutes, n = 3). In a second series of experiments, degradation of an analog (γ-Glu-D-Cys) was tested in rat serum and found to be more stable than the native molecule. The initial velocity for degradation of γ-Glu-D-Cys (0.12 ± 0.02 mM/min; mean ± SD, n = 3) was significantly (P = 0.006) less than that of γ-Glu-Cys (0.22 ± 0.03 mM/min; mean ± SD, n = 3). Furthermore, an in vitro assay indicated that the analog has as an oxidative capacity that equals that of the original peptide in the presence of rat serum and human plasma. Finally, both peptides were found to be similarly effective in preventing lysis of intact cells using in vitro assays. The...
Source: American Journal of Therapeutics - Category: Drugs & Pharmacology Tags: Original Articles Source Type: research

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Alteplase is the only Food and Drug Administration-approved intravenous (IV) thrombolytic medication for acute ischemic stroke. However, multiple recent studies comparing tenecteplase and alteplase suggest that tenecteplase is at least as efficacious as alteplase with regards to neurologic improvement. When given at 0.25 milligrams per kilogram (mg/kg), tenecteplase may have less bleeding complications than alteplase as well. This narrative review evaluates the literature and addresses the practical issues with regards to the use of tenecteplase versus alteplase for acute ischemic stroke, and it recommends that physicians ...
Source: Western Journal of Emergency Medicine - Category: Emergency Medicine Source Type: research
This study aimed to investigate the effects of rTPA in WUS patients during every day clinical scenarios, by measuring ischemic lesion volume and functional outcomes compared to non-treated WUS patients.MethodsWe retrospectively analyzed clinical and imaging data of 149 (75  rTPA; 74 non-rTPA) patients with acute ischemic WUS. Ischemic volume was calculated on follow-up CT and functional outcomes were the NIHSS and mRS comparing rTPA and non-rTPA WUS. Patients were selected using ASPECTS >  6 on CT and/or ischemic penumbra >  50% of hypoperfused tissue on CTP.ResultsA reduced volu...
Source: Journal of Neurology - Category: Neurology Source Type: research
Publication date: November 2019Source: Revista Portuguesa de Cardiologia (English Edition), Volume 38, Issue 11Author(s): Gonçalo J. Morgado, Inês R. Cruz, Ana Catarina Gomes, Ana Rita Almeida, Maria José Loureiro, Carlos Cotrim, Hélder Pereira
Source: Revista Portuguesa de Cardiologia - Category: Cardiology Source Type: research
Publication date: November 2019Source: Revista Portuguesa de Cardiologia (English Edition), Volume 38, Issue 11Author(s): Ahmet Guner, Macit Kalçık, Emrah Bayam, Semih Kalkan, Mehmet Ozkan
Source: Revista Portuguesa de Cardiologia - Category: Cardiology Source Type: research
Ischemic heart disease and stroke are major causes of death and morbidity worldwide. Coronary and cerebrovascular events are a consequence of thrombus formation caused by atherosclerotic plaque rupture or embolism, both of which result from platelet activation and aggregation and thrombin-mediated fibrin generation via the coagulation cascade [1]. In addition, thrombin is also one of the most effective platelet activators [2]. We focused on a novel thrombus formation mechanism called thrombin-mediated platelet stimulation and established thrombin-induced platelet aggregation [3].
Source: Thrombosis Research - Category: Hematology Authors: Tags: Letter to the Editors-in-Chief Source Type: research
ConclusionImaging of thrombus can be used as an aseessment tool to predict the outcomes and it needs further studies in the future.
Source: Neurological Sciences - Category: Neurology Source Type: research
New data from a second EXTEND-IA TNK (tenecteplase) trial clarify the optimum dose of the bolus thrombolytic for use in ischemic stroke, for which enthusiasm is growing.Medscape Medical News
Source: Medscape Cardiology Headlines - Category: Cardiology Tags: Neurology & Neurosurgery News Source Type: news
CONCLUSIONS: Elevated levels of sdLDL-C were associated with a higher prevalence of AIS, especially in non-cardioembolic stroke subtypes. After adjustment for other risk factors, sdLDL-C was found to be an independent risk factor for AIS. Also, sdLDL-C level was strongly associated with AIS severity and poor functional outcomes. Logistic regression models for AIS risk and prognosis prediction were established to help clinicians provide better prevention for high-risk subjects and monitor their prognosis. PMID: 32062644 [PubMed - as supplied by publisher]
Source: Journal of Atherosclerosis and Thrombosis - Category: Cardiology Tags: J Atheroscler Thromb Source Type: research
This study was undertaken to determine whether patients with a PFO would have a significantly increased risk of cerebrovascular accident (CVA) following TKA. The Humana national database was used to identify TKA patients who were stratified by the presence of a PFO from 2007 to 2016. Ninety-day follow-up was used for the primary outcome of CVA. Potential confounding comorbidities also were investigated, including age, sex, anticoagulation, insurance type, arrhythmia, valvular disease, peripheral vascular disease, chronic kidney disease, and diabetes mellitus. Of 153,245 TKAs, a total of 2272 patients had strokes; 479 of th...
Source: Orthopedics - Category: Orthopaedics Authors: Tags: Orthopedics Source Type: research
We report on a patient with acute ischemic stroke secondary to carotid plaque rupture who experienced plaque thrombosis and marked clinical worsening despite IVT. While the latter is the gold standard therapy optimal platelets inhibition should be guaranteed to allow a safe as possible carotid intervention. Hereby we discuss all available strategies to be considered in order to better individualized treatment decision-making.
Source: Journal of Thrombosis and Thrombolysis - Category: Hematology Source Type: research
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