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Glycoprotein (GP)Ib that binds von Willebrand factor (vWF) and glycoprotein (GP)VI, that binds collagen play a significant role in platelet activation and aggregation, and are potential targets for antithrombotic treatment. They are targeted by snake venom proteinases. The effect of a such proteinase, mutalysin-II, on platelet aggregation was examined using washed human platelets and platelet-rich plasma. Its proteolytic activity on vWF, on its binding partner GPIbα, and on GPVI was analyzed by SDS-PAGE, and immunodetection with the corresponding antibodies after blotting. Dose- and time-dependently, mutalysin-II inhibits aggregation of washed platelets induced by vWF plus ristocetin and by convulxin, but with no significant effect on platelet-rich-plasma. Furthermore, mutalysin-II cleaves vWF into low molecular mass multimers of vWF and a rvWF-A1 domain to realease a ∼27-kDa fragment detectable by SDS-PAGE and blotting with mouse anti-rvWF-A1-domain IgG. Moreover, GPVI was cut by mutalysin-II into a soluble ∼55-kDa ectodomain and a fragment of ∼35-kDa. Thus, mutalysin-II inhibits vWF-induced platelet aggregation via cleavage of bound vWF-A1, and its receptor GPIbα. The additional cleavage of, GPVI, blocks collagen-induced platelets. Our data highlight mutalysin-II as an interesting platelet-directed tool targeting vWF-GPIbα binding and particularly GPVI. Thus, it might be suited for antithrombotic therapy as its combined inactivation of two receptors does not significantly compromise hemostasis, but shows high efficacy and safety. Studies are needed to further develop and demonstrate its potential benefits. In normal conditions, platelets circulate through the vasculature in a non-adhesive state. At the site of vascular injury, platelets roll, adhere, and aggregate to arrest bleeding through integrin αIIbβ3. The process of adhesion is orchestrated by the platelet adhesion receptors GPIb that binds von Willebrand Factor and GPVI, which binds collagen, and are potential targets for antithrombotic treatment. They are targeted by SVMPs such as a non-hemorrhagic SVMP mutalysin-II from bushmaster venom. [Display omitted] • Proteolytic cleavage of membrane protein adhesion receptors is regulated by metalloproteinases. • GPVI is a key player when targeted for antithrombotic therapy. • Mutalysin-II targets vWF-GPIbα interaction and GPVI antagonistically. [ABSTRACT FROM AUTHOR]

The coronavirus disease-19 (COVID-19), first appearing in Wuhan, China, and later declared as a pandemic, has caused serious morbidity and mortality worldwide. Severe cases usually present with acute respiratory distress syndrome (ARDS), pneumonia, acute kidney injury (AKI), liver damage, or septic shock. However, with recent advances in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) research, the virus´s effect on cardiac tissues has become evident. Reportedly, an increased number of COVID-19 patients manifested serious cardiac complications such as heart failure, increased troponin, and N-terminal pro-B-type natriuretic peptide levels (NT-proBNP), cardiomyopathies, and myocarditis. These cardiac complications initially present as chest tightness, chest pain, and heart palpitations. Diagnostic investigations such as telemetry, electrocardiogram (ECG), cardiac biomarkers (troponin, NT-proBNP), and inflammatory markers (D-dimer, fibrinogen, PT, PTT), must be performed according to the patient´s condition. The best available options for treatment are the provision of supportive care, anti-viral therapy, hemodynamic monitoring, IL-6 blockers, statins, thrombolytic, and anti-hypertensive drugs. Cardiovascular disease (CVD) healthcare workers should be well-informed about the evolving research regarding COVID-19 and approach as a multi-disciplinary team to devise effective strategies for challenging situations to reduce cardiac complications. [ABSTRACT FROM AUTHOR]

Current research work was performed to evaluate the antioxidant, antidiabetic, thrombolytic, and cytotoxic potential of Bougainvillea glabra leaf extracts with different solvents. Extraction of leaves was carried out by maceration using solvents of various polarity such as n-hexane, chloroform, ethyl acetate, n-butanol, and methanol. The highest values of total phenolic and flavonoid contents were assessed in methanolic extract, such as 58.57% and 29.41%, respectively. Antioxidant potential was measured by DPPH free radical, showing 65.16% scavenging activity in methanolic extract. Similarly, the reducing power of methanolic extract was also measured. Hemolytic activity of B. glabra leaf extracts was evaluated, and maximum percentage lysis was found as 6.86% in chloroform extract. The thrombolytic activity of B. glabra leaf extracts was evaluated against human red blood cells, and the maximum percentage of clot lysis was 59.10% in chloroform extract. Maximum antidiabetic activity (16.20%) was observed in methanolic extract. Overall, the presented results reveal that bogan bail extract is capable of being employed in nutra-pharmaceutical industry. [ABSTRACT FROM AUTHOR]

The purpose of this study was to find the biological propensities of the vegetable plant Pleurospermum candollei by investigating its phytochemical profile and biological activities. Phytochemical analysis was done by spectroscopic methods to investigate the amount of total polyphenols, and biological evaluation was done by the different antioxidant, enzyme inhibitory (tyrosinase, α-amylase, and α-glucosidase), thrombolytic, and antibacterial activities. The highest amount of total phenolic and flavonoid contents was observed in methanolic extract (240.69 ± 2.94 mg GAE/g and 167.59 ± 3.47 mg QE/g); the fractions showed comparatively less quantity (57.02 ± 1.31 to 144.02 ± 2.11 mg GAE/g, and 48.21 ± 0.75 to 96.58 ± 2.30 mg QE/g). The effect of these bioactive contents was also related to biological activities. GCMS analysis led to the identification of bioactive compounds with different biological effects from methanolic extract (antioxidant; 55.07%, antimicrobial; 56.41%), while the identified compounds from the n-hexane fraction with antioxidant properties constituted 67.86%, and those with antimicrobial effects constituted 82.95%; however, the synergetic effect of polyphenols may also have contributed to the highest value of biological activities of methanolic extract. Molecular docking was also performed to understand the relationship of identified secondary metabolites with enzyme-inhibitory activities. The thrombolytic activity was also significant (40.18 ± 1.80 to 57.15 ± 1.10 % clot lysis) in comparison with streptokinase (78.5 ± 1.53 to 82.34 ± 1.25% clot lysis). Methanolic extract also showed good activity against Gram-positive strains of bacteria, and the highest activity was observed against Bacillus subtilis. The findings of this study will improve our knowledge of phytochemistry, and biological activities of P. candollei, which seems to be a ray of hope to design formulations of natural products for the improvement of health and prevention of chronic diseases; however, further research may address the development of novel drugs for use in pharmaceuticals.

Fibrinolytic enzymes are the most effective agents for the treatment of thrombotic diseases. In the present study, we purified and characterized an extracellular fibrinolytic serine metalloprotease (named Velefibrinase) that is produced by marine Bacillus velezensis Z01 and assessed its thrombolysis in vivo. SDS-PAGE and MALDI-TOF-MS analyses showed that the molecular mass of Velefibrinase was 32.3 KDa and belonged to the peptidase S8 family. The optimal fibrinolytic activity conditions of Velefibrinase were 40 °C and pH 7.0. Moreover, Velefibrinase exhibited high substrate specificity to fibrin, and a higher ratio of fibrinolytic/caseinolytic (1.48) values, which indicated that Velefibrinase had excellent fibrinolytic properties. Based on the degradation pattern of fibrin and fibrinogen, Velefibrinase could be classified as α/β-fibrinogenase. In vitro, Velefibrinase demonstrated efficient thrombolytic ability, anti-platelet aggregation, and amelioration of blood coagulation (APTT, PT, TT, and FIB), which were superior to those of commercial anticoagulant urokinase. Velefibrinase showed no hemolysis for erythrocyte in vitro and no hemorrhagic activity in vivo. Finally, Velefibrinase effectively prevented mouse tail thrombosis in a dose-dependent (0.22–0.88 mg/kg) manner. These findings suggested that Velefibrinase has the potential to becoming a new thrombolytic agent.

Background: Thrombolytic therapy significantly improves outcomes among patients with acute ischemic stroke. While cancer outcomes have dramatically improved, the utilization, safety, and mortality outcomes of patients with cancer who receive thrombolytic therapy for acute ischemic stroke are unknown. Methods: Using a national database, we identified all hospitalizations for acute ischemic stroke requiring thrombolytic therapy between 2003 and 2015. Patients with contraindications to thrombolytic therapy were excluded. Following propensity score matching for comorbidity burden, trends in thrombolytic therapy use and its effect on in-hospital mortality, intracranial or all-cause bleeding, and the combined endpoint of mortality and all-cause bleeding, by presence/absence of cancer were evaluated. We also evaluated 30- and 90-day readmission rates post-thrombolytic therapy administration. Results: We identified 237,687 acute ischemic stroke hospitalizations requiring thrombolytic therapy, of which 26,328 (11%) had an underlying cancer. Over the study period, thrombolytic therapy use increased across all acute ischemic stroke admissions, irrespective of cancer presence (12.4/1000 in 2003 to 81.1/1000 in 2015, P < 0.0001). However, thrombolytic therapy utilization differed by cancer presence (4.8% cancer vs.·5.1% non-cancer, P = 0.001). There was no difference in intracranial bleeding (9.6% vs. 9.7%), all-cause bleeding (13.2% vs. 13.2%), or in-hospital mortality (7.6% vs. 7.2%). While there was no difference in 30-day readmission rates by cancer presence (24% vs. 29%, P = 0.40), at 90-days, cancer patients saw higher readmission rates (17.2% vs. 13.3%, P = 0.02). Conclusions: Contemporary thrombolytic therapy use for acute ischemic stroke has risen, irrespective of presence of cancer. Yet, patients with comorbid cancer appear to see lower rates of thrombolytic therapy use for acute ischemic stroke, despite no difference in the rate of intracranial bleeding or mortality after adjustment for comorbidities. [ABSTRACT FROM AUTHOR]

Piper nigrum L. also called black pepper is popular for its numerous uses. The present research is designed to investigate the pharmacological potential of methanol extract of Piper nigrum (MEPN). The antidepressant investigation was performed by using both in vivo forced swimming test (FST) and tail suspension test (TST) methods while the anxiolytic research by hole‐board test (HBT) method. Again, the antipyretic analysis was conducted through yeast‐induced pyrexia method, whereas clot lysis activity was employed by the thrombolytic method. Furthermore, in silico studies followed by molecular docking analysis of several secondary metabolites, pass prediction, and ADME/T were evaluated with AutoDock Vina, Discovery Studio 2020, UCSF Chimera software PASS online, and ADME/T online tools. The plant extract demonstrated dose‐dependent potentiality in antidepressant, anxiolytic, antipyretic, and thrombolytic activities. Induction of MEPN produced a significant (p <.5, p <.001) increase of mobility in FST and TST, and increased the head dipping and decreased the latency of time (p <.01, p <.001) in HBT. MEPN 400 (mg/kg; b.w.; p.o.) lowered the rectal temperature of yeast‐induced pyrexia substantially (p <.001). Besides, MEPN produced promising (p <.001) clot lysis activity. In the computational approach, among all the proteins, a docking score was found ranging from −1.0 to −7.90 kcal/mol. Besides, all the compounds were found safe in ADME/T study. The results of our scientific research validate the suitability of this plant as an alternative source of novel therapeutics. [ABSTRACT FROM AUTHOR]

Endovascular mechanical thrombectomy effectively removes occlusive thrombi from the arterial lumen; however, there is little literature supporting the relevance of vascular geometry on surgical outcomes. Critical vessel characteristics including the degree of angulation and tortuosity influence the ability to advance stent retriever devices toward the site of occlusion. Therefore, it is crucial to evaluate the impact of carotid artery catheter pathway accessibility on the thrombectomy outcomes in acute ischemic stroke (AIS) patients. Traditional imaging modalities generate incomplete pictures of the vascular tortuosity and are prone to clinical judgment errors. Recent three-dimensional computed tomography angiography image analysis techniques circumvent these limitations to calculate accurate tortuosity and angulation measurements. These novel images facilitate classifying common anatomical variant patients into groups that may be treated with specially designed catheter devices. Importantly, this image analysis method reveals significant angulation in the common carotid artery and extracranial internal carotid artery that correlates with delays in reaching the occlusion site. Increased age, which is associated with increased risk of stroke, also increases the incidence of severe tortuosity. The semi-automated measurements technique also demonstrate that full 360° arterial loops are present in nearly 3% of catheter pathways and that the overall degree of angulation differs bilaterally. In this review, we examine the utility of this novel image analysis procedure and evaluate the recent literature relevant to neuroendovascular thrombectomy in AIS patients. Three literature databases - PubMed, Embase, and Web of Science were queried for original articles investigating both preclinical and clinical thrombectomy applications. [ABSTRACT FROM AUTHOR]

Aims: To assess the cytotoxicity, thrombolytic, anthelmintic and antioxidant activity of mehanol extract of Litsea monopetala (Family: Lauraceae) leaves in laboratory using in vitro methods. Methods: Cytotoxicity test was done by brine shrimp lethality bioassay where the extract concentration was 400, 200, 100, 50, 25, 12.5, 6.25, 3.125, 1.5625, 0.78125 (µg/ml). In vitro thrombolytic activity of Litsea monopetala was performed by clot lysis method using extract concentration 2.5, 5, 10 and 20 (mg/mL) in saline water. Anthelmintic activity test was done by using adult earthworms where 10, 20, 40, 60, 80 (mg/ml) extract concentration were used. Finally antioxidant activity was determined by total phenolic content determination using Folin-Ciocalteu reagent. Result: The Litsea monopetala extract showed cytotoxic activity against brine shrimp nauplii and LC50 value was 41.05(µg/ml) and the investigated thrombolytic activity in our research was 9.52, 9.49, 13.64 and 17.50% respectively as% of clot lysis. The paralysis time were at 76.75 min, 60 min, 51.75 min, 44.5 min and 64.5 min and death were at 90.50min, 63.75min, 55.50min, 44.75min and 71min. respectively. The Litsea monopetala extract displayed significant antioxidant activity which was 20.75 (mg of GAE / gm) of extracts. Conclusions: The activities observed could be attributed to presence of some of the phytochemicals which have been related with cytotoxic, thrombolytic, anthelmintic and antioxidant property. [ABSTRACT FROM AUTHOR]

Plant alkaloids are nitrogen containing secondary metabolites that have wide range of biological properties including anticancer activity. ' Lasiosiphon glaucus', or ' Gnidia glauca (Fresen.) Gilg,' known for its biological properties, requires exploration to evaluate cytotoxic and anticancer effects. The present study is aimed to evaluate L. glaucus leaf alkaloid extract (LgLAE) for antimitotic, thrombolytic, and cytotoxic properties. LgLAE demonstrated comparable antimitotic efficacy to methotrexate in Allium cepa root meristematic cells. Thrombolytic evaluation showed a maximum observed clot lysis of 41.39 ± 0.21% at 2 mg/100 µL. Cytotoxicity assay shows greater inhibition of MCF-7 (144.51 μg/mL) cancer cell proliferation than MCF-10A cells (409.86 μg/mL), indicating potential cancer-specific effects. Computational analysis revealed strong binding affinities between L. glaucus alkaloids (Ergocristine, Solasodine, Solanocapsine, Delphinine, and Harmidine) and relevant receptors. These findings highlight L. glaucus contains valuable natural compounds with pharmacological effects, particularly in antimitotic, thrombolytic, and cytotoxic effects, it essential for further investigation for cancer treatment.

Bischofia javanica (Blume), an edible wild plant, has both prospective nutraceutical and therapeutic properties. Here, we intended to explore the pharmacological potentials of the methanol extract of B. javanica (MEBJ) through integrated approaches. Phytochemical screening revealed the presence of important phytoconstituents which were found to be safe during cytotoxicity analysis. The sedative potential of MEBJ (200 and 400 mg/kg) was determined by employing open field, hole cross, and thiopental sodium-induced sleeping time tests, where a significant reduction of the locomotor performance and an enhancement in the duration of sleeping have been observed, respectively. In addition, mice treated with MEBJ exhibited superior exploration during both elevated plus maze and hole board tests. In parallel, anti-diabetic potency was investigated via alpha-amylase inhibitory assay, where a dose-response increase in the percentage of inhibition has been marked. A similar response, such as an increased percentage of clot lysis, was observed during the thrombolytic test. Furthermore, molecular docking was performed with the identified compounds, demonstrated strong binding affinities to the target receptors of the experiments as mentioned above. Also, ADME/T and toxicological parameters verified the drug-like properties of the identified compounds. Collectively, these results indicate bioactivity of Bischofia javanica, which can be a potential candidate in the food and pharmaceutical industries.

Adenia trilobata, locally known as akandaphal in Bangladesh, has some traditional uses. Leaves and stems extracted with pure methanol (MEATL, MEATS) and fractioned by n-hexane (NFATL, NFATS), which was subjected to qualitative phytochemical analysis. The qualitative phytochemical analysis of four extracts showed the presence of secondary metabolites such as alkaloid, carbohydrate, glycosides, flavonoids, phenols, flavonol, and saponins. All four extracts of A. trilobata, exhibited a strong antioxidant activity while a moderately (MEATS = 328 μg/mL) to weakly toxic (NFATL = 616.85 μg/mL) LC50 observed in brine shrimp lethality bioassay. In thrombolytic test, MEATL (18.54 ± 2.18%; P

Medicinal plants are the major sources of traditional treatment of disease in Indian subcontinent due to abundant presence of plants and vast side effects of synthetic drug. The present study was subjected to observe in vitro thrombolytic, antibacterial, and in vivo antidiarrheal activities of methanol soluble fraction of fruits of Annona muricata. In thrombolytic activity assay, various concentrations (2 ─ 10 mg/ml) of methanol soluble fraction was used and dose dependently less potent activity was found. The maximum clot lysis 18.33% (p* < 0.05) was achieved at 10 mg/ml of methanolic fruit extract, whereas standard drug streptokinase showed 55.50% (p*** < 0.001) clot lysis. In antibacterial assay, disc diffusion method was used comprising two gram positive (S. aureus and Micrococcus luteus) and two gram negative (E. coli and P. aeruginosa) bacteria. None of four (0.25, 0.5, 1, and 5 mg/disc) concentration of fruit extract showed antibacterial potentiality, whereas standard amikacin (3 mg/disc) revealed strong antibacterial activities (=~ 23 ─ 24 mm of MIC). To evaluate antidiarrheal activity, castor oil induced diarrhea was created in Swiss albino mice and different doses (100, 200, and 400 mg/kgbw) of fruit extract was introduced post orally. All of three different doses of fruit extract showed significant (p < 0.05 ─ 0.001) antidiarrheal activities. Notably, the percent inhibition of diarrhea by methanolic extract of fruits of Annona muricata was found to be 58.38% at a dose of 400 mg/kgbw. The effect of vehicle saline (10 ml/kgbw) was considered as control and loperamide (5 mg/kgbw) as standard that provided 67.01% inhibition of diarrhea. The results suggest that, the fruits of Annona muricata possess potent antidiarrheal properties, providing scientific basis of using the plant parts in the treatment of diarrheal disease.

The present study was cherished to investigate in vitro thrombolytic, membrane stabilizing and antibacterial activities of Allamanda neriifolia and Aegialitis rotundifolia. Different types methanolic extracts of these two medicinal plants were tested for determining membrane stabilizing activity at a hypotonic solution and heat induce condition by comparing with reference standard acetyl salicylic acid (0.10 mg/mL), where thrombolytic activity assessment was done by employing Streptokinase as standard drug. Finally, antibacterial activity was performed against Staphylococcus aureus as a Gram-positive (+ve) and Salmonella typhi, Escherichia coli and Pseudomonas aeruginosa as Gram negative (−ve) bacteria by using disc diffusion method. In case of membrane stabilizing studies, crude methanolic extracts of A. neriifolia at 10 mg/ml concentration, more importantly, showed 45.80% & 23.52% whereas 10 mg/ml concentration of A. rotundifolia more significantly (p

Objectives: To produce nattokinase in a food-grade expression system and evaluate its thrombolytic activity in vitro. Results: No nattokinase activity from reconstituted strains was observed in simulated gastric juice, but the enzyme was stable in intestinal fluid, the relative activity of which was found to be 60% after 4 h. Due to the nattokinase being produced intracellularly by recombinant bacterial strains, the persistence of the bacteria in gastric juice ensured transmission of the nattokinase into intestinal juice. Because of subsequent disintegration of the bacteria, the highest nattokinase activity was observed after 3 h at approximately 32%, following its carriage within the recombinant strains to the intestinal fluid. Conclusions: This study demonstrated that nattokinase from recombinant strains exhibited good thrombolytic activity in vitro and may be used by the dairy fermentation industry for the development of novel thrombolytic functional foods. [ABSTRACT FROM AUTHOR]

Present work reports the green synthesis of chitosan functionalized silver nanoparticles (CS-AgNPs) using ethanolic buds extract of Sygyzium aromaticum. CS-AgNPs were characterized physically, evaluated for antibacterial, anticoagulant and antiplatelet activities, and toxicity profile. The physical characterization of CS-AgNPs was done by UV/vis, SEM, TEM, FTIR and EDX. The sphericity was found uniform. FTIR and EXD showed noninterfering few impurities. The antibacterial activity against VRSA (ZI, 23.2 ± 0.51 mm) and MRSA (ZI, 25.8 ± 0.32 mm) were determined. The rise in bleeding and thromboplastin was observed highly significant while increased in prothrombin and activated partial prothrombin time in significant manner at both the doses of CS-AgNPs (0.025 mg/kg and 0.05 mg/kg). Reduction in the levels of fibrinogen was also highly significant. Platelet aggregation decreased at high dose of CS-AgNPs i.e. 55.14 ± 8.25% (arachidonic acid) and 13.06 ± 2.17% (collagen). Thrombin antithrombin (TAT) complex activity was found highest for CS-AgNPs. Cytotoxicity was assessed using HeLa cell lines (LC 50 ; 125 μg/ml) and brine shrimp lethality tests (LC 50; 518 μg/ml). The work suggests that green synthesized chitosan functionalized silver nanoparticles may be utilized as an effective antibacterial agent and anticoagulant with low toxicity. The current findings will open a new window for nanomedicine development and future clinical application. • Green synthesis of chitosan functionalized silver nanoparticles (CS-AgNPs) using ethanolic buds extract of Sygyzium aromaticum. • Physical characterization of CS-AgNPs by UV/vis, SEM, TEM, FTIR and EDX. • Antibacterial activity determination using Oxford cup diffusion method against VRSA [LT 0531] and MRSA [LT 4312] and compared with cefoxitin and vancomycin. • Effect of doses of CS-AgNP (0.025 mg/kg and 0.05 mg/kg) and SAEE (125 mg/kg and 250 mg/kg) on bleeding, thromboplastin, prothrombin and activated partial prothrombin time was determined. • Platelet aggregation test, fibrinogen levels and TAT complex activity was also evaluated and LC 50 was calculated using HeLa cell lines and brine shrimp lethality tests. [ABSTRACT FROM AUTHOR]

Herbal medicines have always been in practice since ancient times due to their ease and efficiency. Therefore, methanolic, acetonic, chloroform and n-hexane extract from the seeds of Centratherum anthelminticum were prepared by soxhlet extraction method. These extracts were subjected to quantify antioxidant abilities like TPC, TFC, DPPH free radical scavenging, reducing power, radical scavenging capacity for hydroxyl and nitric oxide. The toxicity of the extract was assessed by hemolytic assay in vitro on human and poultry erythrocyte. However, the percentage clot lysis behaviour of these extracts was also analyzed by thrombolytic activity by using Clopidogrel as standard. Further, Antiviral effect was inspected by in ovo analysis against Newcastle disease virus (NDV). Seven groups of nine-day-old embryonic chicken eggs were inoculated with different concentrations of extracts. Except for the negative control group; all groups were inoculated with NDV strain and different concentrations of four extracts. Observed the embryo's survival every day. Hemagglutination was done by collecting allantoic fluid from experimental eggs. Results indicated that all the extracts have antioxidant potential and display the highest antiradical behaviour in the pattern of methanolic > acetonic > chloroform > n-hexane. The hemolytic activity showed that all extracts of C. anthelminticum are non/less toxic towards Human and poultry RBCs (< 15%). The amount of clot lysis ranged from 19 to 51% compared to 65% and 6.4%, respectively provide by positive control and negative control. In the case of the methanol extract, the level of clot lysis was the most abundant (51%). In the case of in ovo antiviral assay, the highest survival rate was observed in the methanolic extract at 400μg/mL and acetonic extract at 300μg/mL as they control the NDV activity ultimately, evidenced by the absence of embryo death and HA titre. Chloroform and n-hexane could not inhibit the virus completely. [ABSTRACT FROM AUTHOR]

The key purpose of this experiment was to evaluate the thrombolytic, antioxidant, membrane stabilizing and antimicrobial potentials of crude ethanol extracts (CEE) of whole plant, organic and aqueous soluble fractions (OF & AQSF). CEE showed the highest (44.63%) clot lysis activity compared to streptokinase (64.35%). In DPPH study, petroleum ether soluble fraction (PSF) has exhibited IC50 of 18.83 μg/mL while the standard ascorbic acid was 2.48 µg/mL. AQSF profoundly inhibited the lysis of erythrocytes (66.20%) which was insignificantly different (p > 0.05) to acetylsalicylic acid (71.98%), the reference. However, AQSF showed a significantly stronger level of protection against heat-induced hemolysis (64.80%) as compared with the acetylsalicylic acid (78.90%). CEE, OF and AQSF have displayed reasonable growth of inhibition of tested bacteria compared to negative control and standard drug (77.50 mg of GAE/g). [ABSTRACT FROM AUTHOR]

Intravascular thrombosis is a prime cause of cardiac complications worldwide. Microbial fibrinolytic proteases are of clinical significance in thrombosis treatment. The present study discusses the purification and characterization of a protease from Bacillus cereus S46, ascertaining its in vitro thrombolytic activity against a blood clot. By the three‐step purification involving precipitation, dialysis, and diethylaminoethyl‐cellulose ion‐exchange chromatography, a 12.37‐fold purification of the enzyme to homogeneity was achieved. The apparent molecular mass of the protease was 30 kDa, as found by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. The optimum activity of the enzyme was observed at pH 8.0 and 40°C. The enzyme retained an 82.19% residual activity at pH 8.0 and 40°C for 1 h. The Km and Vmax values of the protease with casein were 0.0027 mM and 9.712 µmol/min, respectively. In an in vitro assay, the purified protease resulted in 97.02% lysis of the blood clot. The fibrinolytic potential of the enzyme, together with its characteristics of being active and stable under near‐physiological conditions, may suggest its application as a therapeutic agent. [ABSTRACT FROM AUTHOR]

This research investigated pharmacological properties mainly the anti-inflammatory, anthelmintic, thrombolytic and anxiolytic potential of methanol extract of Syzygium samarangense (MESS) var. parviflorum. Anti-inflammatory action by bovine serum albumin, egg albumin denaturation and membrane stabilization, anthelmintic by live parasites, thrombolytic by clot lysis and anxiolytic by elevated plus maze (EPM) and light and dark box (LDB) tests were measured. The four targeted pharmacological properties were further justified using the most prevalent compounds, isolated from this plant, to be undergone for their pharmacokinetic property's analyses, sitemap analyses and lignad-receptor interactions by computational models through SwissADME and Schrödinger, 2018 softwares against PDB 6COX, 6D6T, 1JFF receptors. MESS was found to display statistically significant (P < 0.05) inhibition of Bovine Serum albumin and Egg albumin denaturation compared to reference drug diclofenac sodium. Remarkable vermicidal effect on the paralysis and death of anthelmintic parasites was observed at MESS concentration 200 mg/dL. A nondescript clot lysis of MESS compared to streptokinase was evident in in vitro thrombolytic assay. MESS increased the number of times the animal crossed from one compartment to the other and the time spent in the brightly-lit chamber of the LDB. Three-methylchalcone derivatives out of seven MESS compounds were undertaken, based on cut off value and sitemap prediction score, for further ligand-receptor binding efficiency. All these three compounds showed promising docking score, glide emodel and glide energy against PDB 6COX, 6D6T and 1DDJ, plasmin proteins demonstrating the prospects of MESS to be materialized for anti-inflammatory, anthelmintic, and thrombolytic therapeutics with further clarification. [ABSTRACT FROM AUTHOR]

Background: Apart from few small single-center studies, there are limited data about STEMI patients in Egypt. Nineteen Egyptian centers (with and without PCI facilities) participated in this registry with 1356 patients who were compared to 7420 patients from other ESC countries. The aims of this study were to describe the characteristics of patients with STEMI, to assess STEMI management patterns particularly the current use of reperfusion therapies, to evaluate the organization of STEMI networks across Egypt, to evaluate in-hospital patient outcome, and to compare Egyptian patients with other ESC countries. Results: Compared to other ESC countries, Egyptian patients were younger (mean age 55.4 ± 11.3 vs. 62.9 ± 12.4; p < 0.001 and 4.36% vs. 19.41%% were ≥ 75 years old; p < 0.001) with fewer females (18.44% vs. 25.63%; p < 0.001). Egypt had longer median time between symptoms onset and first medical contact: 120.0 (60.0; 240.0) vs.100.0 (50.0; 240.0) p < 0.001. Self-presentation rather than EMS presentation was the mode of admission in 86.06% in Egypt vs. 25.83% in EU countries (p < 0.001). On qualifying ECG, anterior STEMI was in 57.08% in Egypt vs. 45.98% in other countries (p < 0.001). Initial reperfusion therapy was 49.12%, 43.07%, and 7.26% for primary PCI, thrombolytic therapy and no reperfusion in Egypt vs. 85.42%, 7.26%, and 7.82% for EU countries, respectively. In-hospital mortality was 4.65% in Egypt vs. 3.50% in other countries p 0.040 and was 18.87% in no reperfusion vs. 2.10% in primary PCI vs. 4.97% in thrombolysis (p < 0.001) among Egyptians. Patients were discharged on aspirin in 98.61%, clopidogrel in 91.07%, ticagrelor in 7.31%, DAPT in 97.69%, beta blockers in 82.83%, ACE inhibitors in 84.76%, MRAs in 10.01%, and statins in 99.77%. Conclusion: Compared to other ESC countries, Egyptian STEMI patients were younger, more frequently current smokers and diabetics, and had longer time between symptoms onset and first medical contact with more self-presentation rather than EMS presentation. Thrombolytic therapy is still a common reperfusion therapy in Egypt while primary PCI was offered to half of the patients. In-hospital mortality was significantly higher in Egypt and was highest among no reperfusion patients and lowest among PPCI patients. [ABSTRACT FROM AUTHOR]

The present study was carried out to investigate phytochemical, antioxidant; antimicrobial, thrombolytic activity and estimate total phenolic, total flavonoid content of Pandanus odoratissimus (P. odoratissimus) leaves of methanol extract. In thrombolytic activity, aqueous soluble fraction (AQSF) exhibited highest percentage (46.58%) of potential to lyse blood clot compared to standard drug streptokinase (69.52%). In antimicrobial assay, dichloromethane soluble fraction (DCMSF) explored the highest diameter of clear zone of inhibition against both gram positive (19.60 ± 0.12 mm) and gram negative (20.00 ± 0.20 mm) bacteria compared to standard antibiotic, Kanamycin (50.00 ± 0.19). Levels of antioxidant were determined by DPPH assay followed by calculated IC50 values of different Kupchan extracts. The methyl soluble fraction (MSF) showed the lowest level of IC50 value (36.70 ± 0.32 µg/mL) in comparison to ascorbic acid (12.48 ± 0.09 µg/mL) while MSF disclosed the maximum level (62.19 ± 0.26 mg of GAE/g of extract) of total phenolic content in the extracts of P. odoratissimus. This study was conducted to validate the P. odoratissimus leaves. [ABSTRACT FROM AUTHOR]

Background: Stuck mechanical heart valves had a debate about the management plan. There is debate regarding the type, dose, and rate of administration of various thrombolytic agents. We report a case with successful thrombolysis using an ultraslow regimen. Case summary: A 43-year-old female with a history of aortic valve (AV) and mitral valve replacement (bi-leaflet metallic valves), and tricuspid valve repair (MINI band) at October 2017. Physical examination showed normal metallic first heart sound and weak metallic second heart sound. Laboratory investigations were normal except low INR, hematocrit, and hemoglobin level (9 gm/L due to iron deficiency anemia). Transthoracic echocardiogram (TTE) and Transoesophageal echocardiogram (TEE) confirmed stuck aortic valve leaflet, with a high mean pressure gradient across prosthetic AV (34 mmHg). The mechanical mitral valve was working well. Fluoroscopy showed stuck one of the AV leaflets in a closed position. The treating physician decided to give her the chance for thrombolytic therapy. This case was treated with ultraslow thrombolytic therapy (Alteplase, 1 mg, every hour) with follow up transthoracic echocardiogram every 24 h to check the pressure gradient on the AV. She was young, asymptomatic, and hemodynamically stable. After 48 h of Alteplase, the stuck leaflet was released. The mean pressure gradient dropped to 16 mmHg. Discussion: Ultraslow thrombolytic regimen advised to be tried in stuck mechanical valves and hemodynamically stable patients. [ABSTRACT FROM AUTHOR]

Background: Chulalongkorn Stroke Center is a comprehensive stroke center (CSC) located in Bangkok, Thailand. Our stroke network consists of different levels of spoke hospitals, ranging from community hospitals where thrombolytic treatment is not available, to those capable of onsite thrombolytic therapy. This study aimed to assess the time to treatment and outcomes among acute ischemic stroke patients who received thrombolytic treatment in the Chulalongkorn Stroke Network by 1.) Direct arrival at the CSC (mothership) 2.) Telestroke-assisted thrombolytic treatment with secondary transfer to the CSC (drip-and-ship) 3.) Referral from community hospital to the CSC for thrombolytic treatment (ship-and-drip).Methods: Acute ischemic stroke patients who received thrombolytic treatment during January 2016-December 2017 in the Chulalongkorn Stroke Network were studied. Time to treatment and clinical outcomes were compared among treatment groups.Results: There were 273 patients in the study including 147, 87, and 39 patients in mothership, drip-and-ship, and ship-and-drip paradigms, respectively. The door-to-needle-time (DTN) and onset-to-needle-time (OTN) times were significantly longest in ship-and-drip group (146.5 ± 62/205.03 ± 44.88 mins) compared to mothership (38 ± 23/155.2 ± 60.54 mins) and drip-and-ship (63.0 ± 44/166.09 ± 87 mins), P < 0.05. There was no significant difference regarding functional independence defined by modified Rankin Scale (mRS) ≤ 2 at 3 months (P = 0.12), in-hospital mortality (P = 0.37), mortality at 3 months (P = 0.73), and symptomatic intracerebral hemorrhage (P = 0.24) among groups.Conclusion: Thrombolytic treatment with drip and ship method under teleconsultation is feasible in Thailand. There was no difference of clinical outcome among the 3 treatment paradigms. However, DTN time and OTN time were longest in the ship-and-drip paradigm. [ABSTRACT FROM AUTHOR]

Background and Purpose: Primary stroke center (PSC) certification is associated with improvements in stroke care and outcome. However, these improvements may reflect a higher baseline level of care delivery in hospitals eventually achieving certification. This study examines whether advancements in acute stroke care at PSCs are due to certification or factors intrinsic to the hospital. Methods: Data was obtained from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial with participation of 40 Emergency Medical System agencies, 315 ambulances, and 60 acute receiving hospitals in Los Angeles and Orange Counties. Subjects were transported to one of three types of destinations: PSC certified hospitals (PSCs), hospitals that were not PSCs at time of enrollment but would later become certified (pre-PSCs), and hospitals that would never be certified (non-PSCs). Metrics of acute stroke care quality included time arrival to imaging, use of intravenous tPA, and arrival to treatment. Results: Of 1,700 cases, 856(50%) were at certified PSCs, 529(31%) were at pre-PSCs, and 315 (19%) were at non-PSCs. Mean (SD) was 33min (±76.1) at PSCs, 47(±86.6) at pre-PSCs, and 49(±71.7) at non-PSCs. Of 1,223 cerebral ischemia cases, rate of tPA utilization was 43% at PSCs, 27% at pre-PSCs, and 28% at non-PSCs. Mean ED arrival to thrombolysis was 71(±32.7) at PSC, 98(±37.6) at pre-PSC, and 95(±45.0) at non-PSCs. PSCs had improved time to imaging (p = 0.014), percent tPA use (p < 0.001), and time to treatment (p = 0.003). Conclusions: Stroke care at hospitals prior to PSC certification is equivalent to care at non-PSCs. Clinical Trial Registration : http://www.clinicaltrials.gov. Unique identifier: NCT00059332. [ABSTRACT FROM AUTHOR]

Objective: Certain bleeding risk scores have been proposed to predict major bleeding (MB) events in patients with acute pulmonary embolism (APE) during anticoagulation therapy. Since patients who undergo thrombolytic treatment are usually excluded from such studies, it is unknown whether these scores may provide an adequate prognostic value for in-hospital major MB. Consequently, we evaluated some well-known bleeding scores to predict in-hospital MB in patients with APE who were treated with thrombolytic therapy. Materials and Methods: A total of 99 consecutive patients with APE who underwent thrombolytic therapy from June 2011 to August 2015 were included in the retrospective study. For each patient, we estimated the bleeding risk using the Kuijer, Riete, Atria, Has-Bled, and PRECISE-DAPT scores. Results: In total, 22 MB events occurred in 99 (19%) patients following admission. A receiver operating characteristic curve analysis showed that the PRECISE-DAPT score might have an adequate prognostic value for MB (area under curve [AUC] value, 0.770). Meanwhile, the other abovementioned risk scores had poor predictive values (AUC values, 0.612-0.658) for MB. Conclusion: Despite being developed and validated to determine MB in patients receiving dual antiplatelet treatment, the PRECISE-DAPT score may be useful in estimating the risk of MB in patients with APE who underwent thrombolytic therapy. [ABSTRACT FROM AUTHOR]

Humans are experiencing serious health issues like myocardial infarction and diabetes. Thrombosis is the reason of myocardial infarction that may cause death. Bioactive compounds or enzymes can be used to dissolve the clot. Whereas diabetes is a disorder of metabolism in which the level of glucose in blood becomes high. It can be controlled by inhibiting a-amylase enzyme. The current project was, therefore planned to investigate the thrombolytic, a-amylase inhibitory and cytotoxic (to access drug safety) potentials of the organic and aqueous bioactive fractions of Bacillus clausii KP10. The cytotoxicity was assessed with hemolytic assay, a-amylase inhibition assay was done by using DNS and in-vitro thrombolytic effect was checked with human blood. In our experiments, the maximum hemolytic activity was shown by ethyl acetate fraction (12.64%). Results were compared with standard Triton X-100 which showed 91.61% hemolytic activity whereas all other fractions showed least cytotoxic activity. The extracts were also evaluated as thrombolytic agents as correlated to streptokinase (73.83%). All the extracts showed clot lysis activity, among which water soluble fraction exhibited maximum (35.16%) clot lysis activity. In our experiment methanol soluble fraction of B. clausii KP10 showed maximum 26.49% a-amylase inhibitory activity. Results were analyzed statistically through analysis of variance (ANOVA). [ABSTRACT FROM AUTHOR]

This investigation was designed and performed to compare the phytochemical profiling, activities of antibacterial, thrombolytic, anti-inflammatory, and cytotoxicity of methanol extract (ME-E) and aqueous extract (AQ-E) of aerial parts of Achyranthes aspera through in-vitro approach. Also characterize the functional groups of bioactive compounds in the ME-E through Fourier-transform infrared (FTIR) spectroscopy analysis. Interestingly, qualitative phytochemical screening proved that the ME-E contain more number of vital phytochemicals such as phenolics. saponins, tannins, alkaloids, flavonoids, cardiac glycosides, steroids, and phlobatannins than AQ-E. Similarly, the ME-E showed notable antibacterial activity as dose dependent manner against Bacillus subtilis , Escherichia coli , Staphylococcus aureus , Klebsiella pneumoniae , and Pseudomonas aeruginosa at 1000 μg mL−1 concentration. ME-E also showed 75.2 ± 2% of clot lysis (thrombolytic activity) at 1000 μg mL−1 dosage and it followed by AQ-E 51.24 ± 3%. The ME-E showed moderate and AQ-E demonstrate poor anti-inflammatory activity evidenced by albumin denaturation inhibition and anti-lipoxygenase assays. Furthermore, the ME-E demonstrated a dose dependent cytotoxicity was noted against brine shrimp larvae. In support of this ME-E considerable activities, the Fourier transform infrared (FTIR) analysis confirmed that this extract contain more number peaks attributed to the stretch of various essential functional groups belongs to different bioactive compounds. Hence this ME-E of A. aspera can be considered for further in depth scientific investigations to validate their maximum biomedical potential. • Methanol extract (ME-E) of A. aspera aerial part contain more phytochemicals. • ME-E and AQ-E yielded 14.2 g as well as 9.5 g of blackish-green coloured paste. • Dose dependent antibacterial activity noted for ME-E with notable MIC value. • ME-E has fine thrombolytic activity and cytotoxicity (brine shrimp) than AQ-E. • FTIR analysis evidenced that the ME-E has more number of bioactive substances. [ABSTRACT FROM AUTHOR]

Tenecteplase (TNK) is emerging as an alternative to alteplase (ALT) for thrombolytic treatment of acute ischemic stroke (AIS). Compared to ALT, TNK has a longer half-life, shorter administration time, lower cost, and similarly high efficacy in treating large vessel occlusion. Nevertheless, there are barriers to adopting TNK as a treatment for AIS. This study aimed to identify thematic barriers and facilitators to adopting TNK as an alternative to ALT as a thrombolytic for eligible AIS patients. Qualitative research methodology using hermeneutic cycling and purposive sampling was used to interview four stroke clinicians in Texas. Interviews were recorded and transcribed verbatim. Enrollment was complete when saturation was reached. All members of the research team participated in content analysis during each cycle and in thematic analysis after saturation. Interviews were conducted between November 2022 and February 2023 with stroke center representatives from centers that either had successfully adopted TNK, or had not yet adopted TNK. Three themes and eight sub-themes were identified. The theme "Evidence" had three sub-themes: Pro-Con Balance, Fundamental Knowledge , and Pharmacotherapeutics. The theme "Process Flow" had four subthemes: Proactive, Reflective self-doubt, Change Process Barriers, and Parameter Barriers. The theme "Consensus" had one sub-theme: Getting Buy-In. Clinicians experience remarkably similar barriers and facilitators to adopting TNK. The results lead to a hypothesis that providing evidence to support a practice change, and identifying key change processes, will help clinicians achieve consensus across teams that need to 'buy in' to adopting TNK for AIS treatment. [ABSTRACT FROM AUTHOR]

Introduction: In order to determine if time from onset to treatment time (OTT) to alteplase (tPA) administration is associated with improved outcomes in acute ischemic stroke, we performed a retrospective analysis of all acute ischemic stroke patients who received tPA at our hospital.Methods: We performed a retrospective review of our Get With the Guidelines® stroke data to determine OTT was associated with either 1.) modified Rankin scale (mRS) at 90 days or 2.) in hospital hemorrhagic conversion. OTT was examined both as a continuous variable in univariate and multivariate analyses as well as a dichotomous variable with a cutoff of 60 min. We controlled for demographic characteristics, 24 medical history issues, receipt of thrombectomy, and NIH stroke scale at admission.Results: We included 166 patients with data for mRS at 90 days after discharge and 302 patients for hemorrhagic conversion in hospital. In all analyses, there was no difference between OTT in either outcome. Predictors of improved mRS at 90 days included NIH Stroke Scale at admission, age, and lack of hypertension. The only significant predictors for hemorrhagic conversion was NIH stroke scale at admission.Conclusion: Our small, retrospective data shows no association between OTT and either hemorrhagic conversion or mRS at 90 days. This data lends support that time may not be the ideal indicator for identifying patients who will benefit from tPA administration. [ABSTRACT FROM AUTHOR]

Objective: Cold methanolic extract of Suaeda maritima have been considered to screen their biological properties such as analgesic, membrane stabilizing and thrombolytic activity. Although some investigations have previously been reported with this plant, the whole plant was not studied yet to date. In the present study we aimed to investigate in vivo and in vitro bioactivities of Suaeda maritima.Material and Methods: The pharmacological analgesic activity was studied by acetic acid induced writhing method in vivo in a mouse model. Membrane stabilizing activity was assessed by inhibition of haemolysis at hypotonic solution induced condition in vitro, and thrombolytic activity was evaluated by employing Streptokinase as standard in vitro.Results: Extract of Suaeda maritima at a dose of 500 mg/kg body weight showed most significant inhibition of writhing at a rate of 82.25% in mice. Among all the fractions, crude methanol extract (ME) showed maximum effect with a value of 61.01% inhibition of hemolysis at 10 mg/ml dose, when standard acetyl salicylic acid (0.10 mg/mL) revealed 66.37% inhibition of hemolysis. When clots were treated with 100 μl, moderate clot lysis activity observed with each of the test sample, however highest effect was found at 10 mg/ml dose (49.13%).Conclusion: The Suaeda maritima extract showed a remarkable analgesic effect on a mouse model and membrane stabilizing and trombolytic activities in vivo models. It may introduce a new dimension in human model in analgesic, membrane stabilizing and antitrombolytic activities.

Deep vein thrombosis (DVT) is a major health problem affecting a significant portion of population. Primary complications are Pulmonary Embolism (PE) in the short term and Post-Thrombotic Syndrome (PTS) in the long term. Thrombolytic drugs act by activating plasminogen which in turn forms the enzyme plasmin. Plasmin consequently degrades blood clots by breaking down the fibrin molecules which make up the clots help to degrade the already formed clot. They can be used using different route of administration, doses and durations. The purpose of this systematic review was to assess the outcome of thrombolytic therapy in terms of the efficacy, safety and effectiveness of the medicines. Electronic searches of databases (MEDLINE and Google Scholar) were queried for articles written in English since 2000 GC. A total of 760 results were obtained using the search keys, and after excluding duplicates, 275 articles were selected. Finally, 9 randomized controlled trials (RCTs) which met the language of publication, study design and exclusion criteria were included in this systematic review. The data were obtained from nine trials (6 countries), providing a study-level data of 1309 participants. Almost all studies revealed that thrombolytic treatment was effective in the management of acute DVT. In most of the studies, the rate of rethrombosis was lower in case of thrombolytic than standard management. Hence, addition of thrombolytic results in persistence and increases the clinical benefits. Thrombolytic therapy was very effective in reversing closed veins, in boosting the patency rate, while reflux was higher in patients treated with anticoagulants. Thrombolytic offers potential advantages over the standard treatment of DVT by reducing the proportion of patients with chronic disabling leg symptoms (such as PTS) by triple in the longer term. However, the incident of major bleeding was higher in patients receiving thrombolytics

Sterculia foetida, also known as jangli badam in Bangladesh, is a traditionally used plant that has pharmacological activities. A qualitative phytochemical analysis was performed to assess the metabolites in a methanolic extract of S. foetida seeds (MESF), and the cytotoxic, thrombolytic, anti-arthritics, analgesic, and antipyretic activities were examined using in vitro, in vivo, and in silico experiments. Quantitative studies were performed through gas chromatography-mass spectroscopy (GC-MS) analysis. The brine shrimp lethality bioassays and clot lysis were performed to investigate the cytotoxic and thrombolytic activities, respectively. The anti-arthritics activity was assessed using the albumin denaturation assay. Analgesic activity was determined using the acetic acid-induced writhing test and the formalin-induced paw-licking test. A molecular docking study was performed, and an online tool was used to perform ADME/T (absorption, distribution, metabolism, and excretion/toxicity) and PASS (Prediction of Activity Spectra for Substances). GC-MS analysis identified 29 compounds in MESF, consisting primarily of phenols, terpenoids, esters, and other organic compounds. MESF showed moderate cytotoxic activity against brine shrimp and significant thrombolytic and anti-arthritics activities compared with the relative standards. The extract also showed a dose-dependent and significant analgesic and antipyretic activities. Docking studies showed that 1-azuleneethanol, acetate returned the best scores for the tested enzymes. These findings suggested that MESF represents a potent source of thrombolytic, anti-arthritic, analgesic, antipyretic agents with moderate cytotoxic effects.

Background: Campsis radicans L. is a flowering plant in Bangladesh, traditionally used for the treatment of several human diseases. In this study, in vitro antioxidant, thrombolytic, membrane stabilizing and in vivo analgesic, hypoglycemic, anti-diarrheal and CNS antidepressant activities of organic soluble fractions of crude methanol extract of C. radicans leaf were investigated using appropriate experimental models. Methods: The leaves of C. radicans were collected, authenticated, dried and extracted with methanol at room temperature for 30 days. The concentrated methanol extract was partitioned to petroleum-ether (PESF), dichloromethane (DMSF) and ethyl acetate (EASF) soluble fractions. The antioxidant activity of these fractions was determined by DPPH free radical scavenging method. Total phenolic content was determined by the Folin-Ciocalteau's spectrophotometric method. The thrombolytic activity was assessed by measuring clot lysis ability whereas the membrane stabilizing activity was evaluated by heat- and hypotonic solution-induced hemolysis assay. Tail immersion procedure and acetic acid- induced writhing model were used to measure the analgesic activity of C. radicans. The hypoglycemic, anti-diarrheal and CNS antidepressant activities were determined by oral glucose tolerance test, castor oil-induced diarrheal model and thiopental-sodium induced sleeping time test in mice, respectively. Results: All the organic soluble fractions of C. radicans contained phenolic compounds varying from 6.38 to 60.13 mg of GAE/gm of extractive, while in DPPH assay, EASF showed the highest free radical scavenging activity with IC50 is 4.69 μg/ml. The PESF exhibited highest thrombolytic activity (57.14% clot lysis) and the DMSF showed maximum 53.95% inhibition of heat-induced hemolysis of human RBCs. In both tail immersion and acetic acid induced writhing models, the PESF, DMSF, EASF at the doses of 200 and 400 mg/kg body weight, induced a significant (P < 0.001) decrease in the painful sensation in mice. Substantial (P < 0.05) anti-hyperglycemic activity of test samples was found in mice loaded with glucose at the same doses mentioned earlier. Castor oil induced diarrheal test of the plant extractives has shown significant effect in comparison to control group. In CNS antidepressant activity assay, the test samples were able to reduce the duration of sleep in mice caused by thiopental administration. Conclusion: All these findings revealed that C. radicans possess significant antioxidant, thrombolytic, membrane stabilizing, analgesic, hypoglycemic, anti-diarrheal and CNS antidepressant activities. [ABSTRACT FROM AUTHOR]

Study Objective: A paucity of data exists on the impact emergency department (ED) pharmacists have on a stroke team's door‐to‐needle (DTN) administration time of recombinant tissue plasminogen activator (rTPA). The purpose of this study was to assess the odds of achieving a DTN administration time for rTPA of 60 minutes or less with an ED pharmacist present. Methods: This was a retrospective, cohort study of patients who received rTPA for acute ischemic stroke (AIS) from May 2017 to May 2018. Patients were included if they were at least 18 years old and received tPA for AIS in the ED. The primary outcome for this study was the likelihood of patients receiving a DTN administration time of 60 minutes or less with or without an ED pharmacist present during a stroke alert at a primary stroke center. Results: The electronic medical record of 184 stroke alert patients was reviewed, and 65 patients were included in the final analysis. Baseline characteristics were similar in all aspects. The odds ratio was 3.3 (95% confidence interval [CI]: 1.1‐9.6; P = 0.04) to achieve a DTN administration time of 60 minutes or less when an ED pharmacist was present. The ED pharmacist present group had faster median (47 minutes vs 60 minutes; P = 0.001) and average (49 minutes vs 63 minutes; P = 0.003) DTN administration times compared with the ED pharmacist not present group. Conclusion: An ED pharmacists present during a stroke alert at our faculty resulted in reduced overall DTN rTPA administration times and increased the odds of a patient receiving rTPA less than 60 minutes from arrival for AIS. Further study is required to determine if this finding can be replicated in other EDs. [ABSTRACT FROM AUTHOR]

This article reports the results of a single-site prospective audit evaluating the safety and effectiveness of urokinase (Syner-Kinase®) to restore patency in central venous access devices (CVADs) for cancer patients. CVADs are routinely inserted to allow the safe and timely administration of systemic anti-cancer therapies; therefore, catheter dysfunction can interrupt the treatment schedule and adversely affect patient outcome. The aim was to contribute to the development of evidence-based, standardised, best practice guidelines. Prospective data were collected from all patients (n=22) identified with an occluded CVAD, requiring use of Syner-Kinase to manage a persistent withdrawal occlusion or total occlusion, over a 6-month period. Findings revealed a single administration of Syner-Kinase for catheter occlusion clearance to be effective in 92% of cases. Results suggest that use of the thrombolytic agent is well-tolerated and an effective means of restoring patency for long-term CVADs in cancer patients. [ABSTRACT FROM AUTHOR]

Deep vein thrombosis (DVT) is a major health problem affecting a significant portion of population. Primary complications are Pulmonary Embolism (PE) in the short term and Post-Thrombotic Syndrome (PTS) in the long term. Thrombolytic drugs act by activating plasminogen which in turn forms the enzyme plasmin. Plasmin consequently degrades blood clots by breaking down the fibrin molecules which make up the clots help to degrade the already formed clot. They can be used using different route of administration, doses and durations. The purpose of this systematic review was to assess the outcome of thrombolytic therapy in terms of the efficacy, safety and effectiveness of the medicines. Electronic searches of databases (MEDLINE and Google Scholar) were queried for articles written in English since 2000 GC. A total of 760 results were obtained using the search keys, and after excluding duplicates, 275 articles were selected. Finally, 9 randomized controlled trials (RCTs) which met the language of publication, study design and exclusion criteria were included in this systematic review. The data were obtained from nine trials (6 countries), providing a study-level data of 1309 participants. Almost all studies revealed that thrombolytic treatment was effective in the management of acute DVT. In most of the studies, the rate of rethrombosis was lower in case of thrombolytic than standard management. Hence, addition of thrombolytic results in persistence and increases the clinical benefits. Thrombolytic therapy was very effective in reversing closed veins, in boosting the patency rate, while reflux was higher in patients treated with anticoagulants. Thrombolytic offers potential advantages over the standard treatment of DVT by reducing the proportion of patients with chronic disabling leg symptoms (such as PTS) by triple in the longer term. However, the incident of major bleeding was higher in patients receiving thrombolytics than anticoagulants. [ABSTRACT FROM AUTHOR]

Amaç: İnme tedavisinde asıl amaç, oklüde vasküler yapının belirli süre içerisinde rekanalizasyonudur. Medikal tedavide rekombinant doku plazminojen aktivatörü (tPA) kullanılmaktadır. Bu çalışmada, tPA tedavisi verilen iskemik inme hastaları değerlendirilmiştir. Gereç ve Yöntem: Temmuz 2015-Ağustos 2017 arasında tPA tedavisi uygulanan 97 akut iskemik inme hastası retrospektif incelendi. Demografik veriler, başvuru semptomları ve tedavi saatleri kaydedildi. Klinik durum ve prognoz 'National Institutes of Health Stroke Skalası' (NIHSS) ve fonksiyonel durum ölçeği ile değerlendirildi. Hemorajik dönüşüm bilgisayarlı tomografiile değerlendirildi. Bulgular: Çalışmaya 61(%62,8) erkek ve 36 (%37,2) kadın hasta alındı. Yaş ortalamaları 60,29±12,62 idi. 7 (%7,2) hastaya 1. saate, 5(%25,8) hastaya 1-2 saat arasında, 31(%32) hastaya 2-3 saat arasında, 34 (%35,1) hastaya 3-4,5 saat arasında tPAbaşlandı. Başvuruda en sık semptom hemi/monoparezi idi (%92,8).%69,1 oranında parsiyel anterior, %16,5 total anterior, %15,8 posterior vasküler oklüzyon saptandı. NIHSS sonuçları 10,39±4,36 (tedavi öncesi) ve 6,63±3,76 (taburculuk) idi. Hastalartam bağımsız (%20,6), kısmi bağımlı (%43,3) ve tam bağımlı (%21,6) olarak taburcu edildi.Hastaların %12'sinde hemorajik dönüşüm izlendi.Platelet değeri düşük olan hastalarda hemorajik transformasyon daha fazlaydı (P<0,05).Hemorajik dönüşüm olan hastalarda mortalite %41,7 idi.Hemorajik dönüşüm gelişimi mortaliteyi artırmaktaydı (p <0,05). Sonuç: İnmede trombolitik tedavi özürlülükte azalma sağlamaktadır. Ancak hemorajik transformasyon mortaliteyi artırmaktadır. Bu da platelet değerindeki düşüklük ile ilişkili olabilir. Objective: The main purpose of treatment in stroke is recanalization of occluded vascular structure within a certain time period. Recombinant tissue plasminogen activator (tPA) is used for medical treatment. In this study, patients with ischemic stroke treated with tPA were evaluated. Material and Methods: Between July 2015 and August 2017, 97 patients with acute ischemic stroke who were treated with tPA reviewed retrospectively. Demographic data, presentation symptoms and treatment times were recorded. Clinical status and prognosis were evaluated with National Institutes of Health Stroke Scale (NIHSS) and functional status scale. Hemorrhagic transformation was evaluated with computed tomography. Results: 61 (62.8%) male and 36 (37.2%) female patients were included to study. The mean age was 60.29±12.62. tPA was started to 7 (7.2%) patients in 1 hour, 25 (25.8%) patients in 1-2 hours, 31 (32%) patients in 2-3 hours, 34 (35.1%) patients in 3-4.5 hours. The most common symptom was hemi/monoparesis (92.8%). 69.1% partial anterior, 16.5% total anterior and 15.8% posterior vascular occlusion were detected. NIHSS results were 10.39±4.36 (pre-treatment) and 6.63±3.76 (discharged). Patients were discharged with not disabilty (20.6%), partial disabilty (43.3%) and major disabilty (21.6%). Hemorrhagic transformation was detected in 12% of patients. Hemorrhagic transformation was higher in patients with low platelets (P<0.05). The mortality in patients with hemorrhagic transformation was 41%. Hemorrhagic transformation increased mortality (p<0.05). Conclusion: Thrombolytic treatment in stroke decreases disability. However, hemorrhagic transformation increases mortality. This may be related to low platelet value. [ABSTRACT FROM AUTHOR]

Phytochemical screening of chloroform and methanolic extracts of different parts of Solanum torvum and Smilax zeylanica was done. In vitro thrombolytic and anti-arthritic activities were assessed using the clot lysis method and egg albumin denaturation technique respectively. Between the chloroform and methanolic extracts, Chloroform extracts of both plants showed higher clot lysis activities (at 100 ppm solution). On the other hand, extracts of both plants performed better in terms of anti-arthritic activities (at 500 ppm solution). In the case of thrombolytic activity, between the plant extracts, the performance of S. torvum is higher compared to S. zeylanica plant. Among chloroform extracts of different plant parts, stem of S. torvum and root of S. zeylanica showed the highest, 35.44±1.89 % and 33.63±0.83 % activities respectively. Whereas, among the methanolic extracts of the plants, the root extracts of both plants showed the highest activities, 31.96±2.86 % for S. torvum and 32.01±1.46 % for S. zeylanica. In the case of anti-arthritic activity, the performance of S. zeylanica plant extracts is higher compared to that of S. torvum. Methanolic extract of leaf of S. zeylanica samples showed the best protein denaturation activity (52.38±2.12 %) followed by the Methanolic extract of stem sample of S. torvum (44.29±2.14 %). [ABSTRACT FROM AUTHOR]

Background/aim: It was aimed to describe the technical aspects and outcomes of percutaneous ultrasound-guided recanalization of thrombosed hemodialysis fistulas by thrombolytic injection. Materials and methods: A retrospective review was performed on patients with thrombosed native hemodialysis fistula who were treated using the percutaneous ultrasound-guided thrombolytic agent injection technique at the interventional radiology department. A total of 17 patients [7 women (41.2%) and 10 men (58.8%)] were included in this study. All of the data, including demographic information and clinical findings, were obtained from the patients' medical records and follow-up form of the procedure. Results: The mean fistula age was 5.6 years (range: 1-15 years). The mean diameter of the thrombosed segment was 5.53 cm (2-10 cm). Localization of the thrombi was in the aneurysmal segment at the level of needle insertion in 64.7% (n: 11) of patients, while it was on the venous side of the anastomosis in 35.3% (n: 6). The mean dose of tissue plasminogen activator (tPA) used in all of the sessions was 8.88 mg (5-17 mg). Overall technical success after all of the administrations was 100% and clinical success was 94.1%. Conclusion: Percutaneous ultrasound-guided thrombolytic injection in native hemodialysis fistulas is a rapid, practical, repeatable treatment method that is received on an outpatient basis with low risk of bleeding, and prevents unnecessary endovascular interventions or surgical operations. [ABSTRACT FROM AUTHOR]

Background: The aim of this experiment was to evaluate the cytotoxic, thrombolytic, analgesic, sedative-hypnotic and anxiolytic activities of the methanolic extract of Ficus cunia leaves. Methods: Primary phytochemical screening was accomplished by using established methods. Cytotoxicity was studied by brine shrimp lethality test, and the thrombolytic assay was conducted through clot lysis method with human blood. The in vivo action was done using mice of both sexes. The analgesic activity was evaluated by acetic acid-induced writhing test and formalin-induced paw licking test. Open field, hole cross and thiopental Na-induced sleeping time test were used to examine the sedative-hypnotic activity, and elevated plus maze (EPM) and hole board test were used to identify the anxiolytic activity. Results: The results elicited that the extract contained several phytochemicals such as alkaloid, flavonoid, and tannin. The extract was found to have a median lethal concentration (LC50) value of 55.48 μg/mL in the brine shrimp lethality bioassay. It was also assessed for antithrombotic activity when compared with streptokinase; it has significant (p < 0.001) thrombolytic effect (34.72 ± 1.74%) contrasted with standard streptokinase (67 ± 1.56%). The extract at doses of 200 and 400 mg/kg produced inhibition of 32.58% and 46.63% in acetic acid-induced pain and 45.88 and 61.18% in formalin-induced pain. The sedative and hypnotic activities on the central nervous system of the methanol extract of F. cunia (MEFC) leaves were evaluated. The extract delivered critical sedative impact at the doses of 200 and 400 mg/kg (by oral route) treated with reference to the substance diazepam, and the hypnotic impact was also observed in the case of mice. MEFC at its maximum dose (400 mg/kg) significantly (p < 0.01) increased the time spent in the open arms of the EPM. In the hole board test, there was a dose-dependent (at 200 and 400 mg/kg) and a significant (p < 0.05 and p < 0.01) increase in the number of head pokes in comparison to control. Conclusions: The results of the present study gave a helpful baseline in progression for the possible use of MEFC as a cytotoxic, thrombolytic, analgesic, sedative-hypnotic and anxiolytic drug. [ABSTRACT FROM AUTHOR]

Introduction: The Clot Lysis: Evaluating Accelerated Resolution of IVH trial examined whether irrigating the ventricular system with alteplase improved functional outcomes in patients with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH). Thalamic ICH location was common and was associated with poor outcome. One possible explanation is thalamic ICH-associated mass effect obstructing the third ventricle. We hypothesized that patients with thalamic ICH obstructing the third ventricle would have worse functional outcomes compared to patients without obstructing lesions.Methods: ICH obstruction of third ventricle was defined as third ventricle compression on 1 or more axial computed tomography slices visually impeding cerebral spinal fluid flow. If the third ventricle was casted with IVH, it was scored as such. Multivariable logistic regression analyses were used to determine whether obstruction of the third ventricle predicts poor functional outcomes defined as modified Rankin score (mRS) 4-6, higher mRS, and mortality at 180 days. Models were adjusted for thalamic ICH location, ICH volume, IVH volume, age, hydrocephalus, baseline Glasgow coma scale, and percentage of low cerebral perfusion pressures during treatment.Results: Among saline-treated patients, obstruction of the third ventricle by IVH was a significant predictor of higher mRS at 180 days (OR 1.87, CI 1.01-3.47) and mortality at 180 days (OR 2.73, CI 1.27-5.87) while obstruction by ICH was not. In contrast, among alteplase-treated patients, obstruction by ICH was a significant predictor of mRS 4-6 (OR 3.20, CI 1.30-7.88) and higher mRS at 180 days (OR 2.33, CI 1.24-4.35), while obstruction by IVH was not.Conclusions: Poor outcomes were associated with mass-related obstruction of the third ventricle from thalamic ICH in alteplase-treated patients and from IVH in saline-treated patients. Once the ventricular system is cleared with alteplase, obstruction of cerebral spinal fluid flow from thalamic ICH might become important in functional recovery. [ABSTRACT FROM AUTHOR]

The leaves of Homalomena aromatica are traditionally used in Bangladesh for the treatment of different chronic ailments. The purpose of this study was to explore in vitro antioxidant, thrombolytic activities, and in vivo neuropharmacological effects of methanolic extract of Homalomena aromatica (MEHA) leaves. Antioxidant activity of MEHA was assessed by a DPPH free radical scavenging assay and total phenolics content, total flavonoids content were also measured. The thrombolytic activity was determined by percentage of clot lysis and neuropharmacological activities by hole board, tail suspension, forced swimming and elevated plus maze tests. The results showed that the IC50 value of the extract against DPPH was 199.51 μg/mL. Quantitative analysis displayed higher contents of phenolics and flavonoids (147.71 mg gallic acid equivalent/g & 66.65 mg quercetin equivalent/g dried extract, respectively). The extract also showed a significant clot lysis (33.31%) activity. In case of anxiolytic activity, the elevate plus maze (EPM) test demonstrated an increase in time spent in open arms, and in case of hole board test, the number of head dipping was also significantly increased (p < 0.05). All the test compared with control (1% Tween in water) and standard (diazepam 1 mg/kg), significant dose (200 & 400 mg/kg) dependent anxiolytic activity was found. In antidepressant activity, there was a significant decrease in period of immobility in both test models (tail suspension and forced swimming) (p < 0.05). Moreover, 13 compounds were identified as bioactive, showed good binding affinities to xanthine oxidoreductase, tissue plasminogen activator receptor, potassium channel receptor, human serotonin receptor targets in molecular docking experiments. Furthermore, ADME/T analysis revealed their drug-likeness, likely pharmacological actions and non-toxic upon consumption. Taken together, our finding support the traditional medicinal use of this plant, which may provide a potential source for future drug discovery.

Syzygium fruticosum (SF), a valuable Bangladeshi fruit, is considered an alternative therapeutic agent. Mainly, seeds are used as nutritional phytotherapy to ease physical and mental status by preventing chronic diseases. Here, we scrutinized the S. fruticosum seed’s fundamental importance in traditional medicine by following an integrated approach combining in vivo, in vitro, and in silico studies. The SF was fractionated with different solvents, and the ethyl acetate fraction of SF (EaF-SF) was further studied. Mice treated with EaF-SF (200 and 400 mg/kg) manifested anxiolysis evidenced by higher exploration in elevated plus maze and hole board tests. Similarly, a dose-dependent drop of immobility time in a forced swimming test ensured significant anti-depressant activity. Moreover, higher dose treatment exposed reduced exploratory behaviour resembling decreased movement and prolonged sleeping latency with a quick onset of sleep during the open field and thiopental-induced sleeping tests, respectively. In parallel, EaF-SF significantly (p < 0.001) and dose-dependently suppressed acetic acid and formalin-induced pain in mice. Also, a noteworthy anti-inflammatory activity and a substantial (p < 0.01) clot lysis activity (thrombolytic) was observed. Gas chromatography-mass spectrometry (GC–MS) analysis resulted in 49 bioactive compounds. Among them, 12 bioactive compounds with Lipinski’s rule and safety confirmation showed strong binding affinity (molecular docking) against the receptors of each model used. To conclude, the S. fruticosum seed is a prospective source of health-promoting effects that can be an excellent candidate for preventing degenerative diseases.

Lepidagathis hyalina Nees is used locally in Ayurvedic medicine to treat coughs and cardiovascular diseases. This study explored its pharmacological potential through in vivo and in vitro approaches for the metabolites extracted (methanolic) from the stems of L. hyalina. A qualitative phytochemical analysis revealed the presence of numerous secondary metabolites. The methanol extract of L. hyalina stems (MELHS) showed a strong antioxidative activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing power assays, and in the quantitative (phenolic and flavonoid) assay. Clot lysis and brine shrimp lethality bioassays were applied to investigate the thrombolytic and cytotoxic activities, respectively. MELHS exhibited an expressive percentage of clot lysis (33.98%) with a moderately toxic (115.11 μg/mL) effect. The in vivo anxiolytic activity was studied by an elevated plus maze test, whereas the antidepressant activity was examined by a tail suspension test and forced swimming test. During the anxiolytic evaluation, MELHS exhibited a significant dose-dependent reduction of anxiety, in which the 400 mg/kg dose of the extract showed 78.77 ± 4.42% time spent in the open arm in the elevated plus maze test. In addition, MELHS demonstrated dose-dependent and significant activities in the tail suspension test and forced swimming test, whereas the 400 mg/kg dose of the extract showed 87.67 ± 6.40% and 83.33 ± 6.39% inhibition of immobile time, respectively. Therefore, the current study suggests that L. hyalina could be a potential source of anti-oxidative, cytotoxic, thrombolytic, anxiolytic, and antidepressant agents. Further study is needed to determine the mechanism behind the bioactivities.