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Timely treatment of stroke patients is critical for improving outcomes. Emergency Department-Stroke Response Units (ED-SRUs) have emerged as effective models for enhancing stroke care. This study aims to describe the implementation and outcomes of a specialty nurse-led ED-SRU staffed by highly trained neuroscience specialty nurses. We analyzed the collaboration between neuroscience and emergency-trained nurses in the ED-SRU and its impact on stroke treatment metrics, focusing on door-to-needle time for intravenous thrombolytics. The implementation of the ED-SRU resulted in a significant reduction in door-to-needle times, allowing the hospital to surpass national benchmarks for timely stroke treatment. The success of the ED-SRU underscores the importance of interdisciplinary nursing in effectively triaging and caring for complex stroke patients. This model can serve as a framework for other institutions aiming to enhance stroke care delivery. [ABSTRACT FROM AUTHOR]

A decade on from the first positive thrombectomy trials, hyperacute therapies for ischemic stroke continue to rapidly advance. Effective treatments remain limited to reperfusion, although several cytoprotective approaches continue to be investigated. Intravenous fibrinolytics are now demonstrated to be beneficial up to 24 h in patients selected using perfusion imaging, but their role in patients with non-disabling symptoms appears very limited. Tenecteplase is superior to alteplase in meta-analysis of the latest trials, and adjuvant thrombolytics are an area of active investigation. Endovascular thrombectomy is beneficial in a wide range of anterior and posterior circulation large vessel occlusions up to 24 h after onset with the more distal occlusions, mild presentations, and >24 h window being the main frontiers to be tested in ongoing trials. Imaging parameters are prognostic but appear not to modify the relative treatment benefit of thrombectomy versus standard medical care. Therefore, deciding who not to treat with thrombectomy is a key clinical challenge that requires careful but rapid integration of clinical, imaging, and patient preference considerations. Systems of care to accelerate delivery of these highly effective therapies will maximize benefits for the greatest number of patients with stroke. [ABSTRACT FROM AUTHOR]

Background and Aims: This study aims to compare the effectiveness of thrombolytic therapy and anticoagulation in preventing chronic thromboembolic pulmonary hypertension (CTEPH). Method: A total of 60 patients with intermediate‐high risk pulmonary embolism (PE) were randomly assigned to receive either thrombolytic therapy (n = 30) or anticoagulation (n = 30). Results: Echocardiographic assessments demonstrated no significant differences between the two treatment approaches in terms of right ventricular size (RVS) (on discharge in thrombolytic group: 31.17 ± 3.43 vs. anticoagulant group: 32.73 ± 5.27, p = 0.912), tricuspid annular plane systolic excursion (TAPSE) (on discharge in thrombolytic group: 17.66 ± 2.39 vs. anticoagulant group: 16.73 ± 2.93, p = 0.290), and systolic pulmonary artery pressure (SPAP) (on discharge in thrombolytic group: 32.93 ± 9.73 vs. anticoagulant group: 34.46 ± 9.30, p = 0.840). However, significant changes were observed in all assessed parameters within each treatment group (p < 0.001). The 6‐month follow‐up showed no significant difference between the two groups in terms of CTEPH incidence (p = 0.781) or functional class of the patients (p = 0.135). Conclusion: Based on the findings of this study, neither thrombolytic therapy nor anticoagulation demonstrated superiority over the other in reducing adverse outcomes associated with intermediate‐high risk PE, including right ventricular size, SPAP, TAPSE, or CTEPH. [ABSTRACT FROM AUTHOR]

The current study aimed to assess the phytochemical profile of Macaranga indica (MI) leaves, as well as their antioxidant, thrombolytic, and neuropharmacological activities. Methanol extract from Macaranga indica (MEMI) Wight leaves was used to investigate these activities to validate the therapeutic profile using a wellestablished method. GraphPad Prism, version 9.4.1 was used to analyze the experimental results. In vitro, the antioxidant DPPH free radical scavenging assay yielded an IC50 value of 9.58 µg/ml. Reducing power capacity showed an increase in absorbance with the increase of different concentrations. Quantitative analyses of phytochemical elicit the presence of phenol (777±12.13), flavonoid (99.94±0.62), flavonol (244±2.53), total antioxidant (184.48±1.92) mg/g in the dry extract. In vitro thrombolytic activity showed a highly statistically significant (P < 0.0001) clot lysis (42.66±3.19%). In vivo antidepressant, anxiolytic, and sedative activities evaluated the statistically significant (P < 0.001 at 200 mg/kg and P < 0.0001 at 400 mg/kg) by decreasing immobility time of forced swimming test, (P < 0.0001) by reducing anxiety of elevated plus maze and hole board test and (P = 0.0106) mice movement were gradually decreasing of hole cross test. These findings indicate that the crude extract of MEMI leaves has significant antioxidant, thrombolytic, and neuropharmacological properties. [ABSTRACT FROM AUTHOR]

Although the conventional usage of Sphaeranthus indicus flowers in medicine exists, there is a lack of research on the precise pharmacological characteristics and comprehensive phytochemical composition of its flowers, resulting in a knowledge gap on their whole therapeutic capabilities. The aim of this work is to identify and describe the phytochemicals found in the flowers of Sphaeranthus indicus and assess specific pharmacological effects, such as antioxidant, antibacterial, anti-inflammatory, thrombolytic, antidepressant, and antidiarrheal characteristics. The investigation revealed that the MESIF (methanol extract of S. indicus flowers) showed substantial antioxidant performance (IC50 = 26.33) accompanied by a moderate phenolic content (93.33 ± 1.76). At 250 and 500 µg/ml, the extract exhibited modest to moderate antibacterial sensitivity against many tested pathogens and significantly reduced inflammation by protein denaturation (41.63 ± 0.11 and 70.52 ± 0.20). Furthermore, MESIF exhibited remarkable thrombolytic activity with a statistically significant (***P [ J Adv Biotechnol Exp Ther 2024; 7(3.000): 642-657]

Abstract The green synthesis of nanoparticles (NPs) gained significant impacts in various fields due to the use of eco-friendly approaches. In this study, silver nanoparticles (AgNPs) were synthesized from the aqueous extract of Hylocereus undatus fruit peel. The presence of AgNPs was analysed using characterization methods such as UV‒Vis, FTIR, GCMS, XRD, EDAX, and FESEM. The synthesized AgNPs showed greater antibacterial activity against Escherichia coli than against Streptococcus pneumoniae. The antifungal activity against Candida albicans was greater than that against Candida tropicalis. The IC50 value for the antibiofilm activity of the AgNPs was 2.81 µg/mL, whereas that of the H. undatus peel extract was 1.34 µg/mL. The invitro antioxidant activity of the AgNPs was evaluated using two different methods. The DPPH radical scavenging activity of the AgNPs and fruit peel extract was observed with IC50 values of 3.8 and 2.03 µg/mL respectively. On the other hand, nitric oxide radical scavenging activities were recorded and the IC50 values were calculated to be 2.8 and 2.3 µg/mL. The AgNPs demonstrated thrombolytic activity in human blood with 10, 32.36, and 56.25% lysis. The cytotoxicity of the AgNPs was minimal, with an IC50 of 0.2 µg/mL and the peel extract had the greatest cytotoxicity with an IC50 of 0.3 µg/mL. The findings of this study demonstrated that the synthesized AgNPs from H. undatus peel extract could be potential candidates for treating prostate cancer. Graphical abstract

Highlights Based on Fe-Hpdca-PDMS and carbon nanotube composite, an optoacoustic patch is developed, which can recover from the damage induced by cutting or laser irradiation at room temperature. The patch has high laser damage threshold (183.44 mJ cm−2) and optoacoustic energy conversion efficiency (10.66×10−3). The patch has been successfully examined in acoustic flow, thrombolysis, and wireless energy harvesting, which may provide new insights into the field of the design and fabrication of novel ultrasound devices for biomedical applications.

Introduction: Natural plant-based medicines have gained popularity recently as a major source of inventive, risk-free, and more potent secondary bioactive compounds with medicinal potential. Catharanthus ovalis is a perennial shrub containing various indole alkaloids cultivated extensively for local medical purposes. Methods: This research is conducted to identify the phytocompounds present in the leaves of C. ovalis and its central and peripheral analgesic, thrombolytic, and membrane-stabilizing activities through tail immersion, acetic acid-induced writhing, human blood clot lysis, and erythrocyte lysis by heat and hypotonic solution methods, respectively. Results and discussion: A total of 39 compounds were identified using GC-MS/MS techniques, including hexadecanoic acid, methyl ester (56.749%), methyl stearate (29.782%), carvacrol and its TBDMS derivative (12.586%), and 9-octadecenoic acid, methyl ester, (E)-] (9.297%) presented in high quantity. The highest tail immersion latency was observed for the 600 mg/kg extract of C. ovalis crude extract. Both 400 and 600 mg/kg doses of C. ovalis crude extract exhibited prominent peripheral analgesic activity. The maximum thrombolytic effect was observed by DCM soluble fraction extract by inhibiting 54.87% of the clot. However, the aqueous-soluble fraction of this extract manifested an excellent membrane-stabilizing effect by showing 73.98% and 87.51% hemolysis against heat- and hypotonic-induced hemolysis, respectively. Some of the compounds were identified as active agents against different receptors related to these diseases, which supported the findings of in vitro and in vivo tests. Conclusion: Further investigation needs to be conducted to specify and identify the exact mechanism of action of these compounds. [ABSTRACT FROM AUTHOR]

Controversy surrounds the optimal therapy for submassive and massive pulmonary embolism (PE). We conducted a systematic review and meta-analysis to compare the outcomes of catheter-directed thrombolysis (CDT) versus surgical and catheter-based thrombectomy in patients with submassive and massive PE. We searched PubMed, EMBASE, Cochrane, and Google Scholar for studies comparing outcomes of CDT versus thrombectomy in submassive and massive PE. Studies were identified and data were extracted by two independent reviewers. A random effects model was used to calculate risk ratios (RRs) with 95 % confidence intervals (CIs). Outcomes included in-hospital mortality, procedural complications, hospital and intensive care unit (ICU) length of stay (LOS), 30-day readmissions, and right ventricle/left ventricle (RV/LV) ratio improvement. Eight observational studies with 1403 patients were included, of whom 50.0 % received CDT. Compared to thrombectomy, CDT was associated with significantly lower in-hospital mortality (RR 0.62; 95 % CI 0.43–0.89; p = 0.01) and similar rates of major bleeding (p = 0.61), blood transfusion (p = 0.41), stroke (p = 0.41), and atrial fibrillation (p = 0.71). The hospital and ICU LOS, 30-day readmissions, and degree of RV/LV ratio improvement were similar between the two strategies (all p > 0.1). In subgroup analyses, in-hospital mortality was similar between CDT and catheter-based thrombectomy (p = 0.48) but lower with CDT compared with surgical thrombectomy (p = 0.01). In patients with submassive and massive PE, CDT was associated with similar in-hospital mortality compared to catheter-based thrombectomy, but lower in-hospital mortality compared to surgical thrombectomy. Procedural complications, LOS, 30-day readmissions, and RV/LV ratio improvement were similar between CDT and any thrombectomy. Randomized controlled trials are indicated to confirm our findings. • Controversy surrounds the optimal therapy for submassive and massive PE. • CDT was associated with similar in-hospital mortality compared to catheter-based thrombectomy. • CDT was associated with lower in-hospital mortality compared to surgical thrombectomy. • CDT and thrombectomy had similar complications, LOS, 30-day readmissions, and RV/LV ratio improvement. • This study expands the evidence supporting CDT as a feasible option for submassive and massive PE. [ABSTRACT FROM AUTHOR]

In the current research, a new therapeutically active ethyl-4-(2,4-methoxyphenyl)-1,2,3,4-tetrahydro-6-methyl-2-thioxopyrimidine-5-carboxylate (DMPC) prepared by the Biginelli reaction was found to possess effective antioxidant and thrombolytic activities. The geometry of the DMPC was confirmed by the single crystal X-ray diffraction analysis and DFT studies carried out by B3LYP6-311++G (d,p) method and the results have been compared with the actual values. The Mulliken charge distribution, molecular electrostatic potential (MEP) surface, HOMO and LUMO of the DMPC were calculated by victimization a similar level theory. NLO of the DMPC was studied from the optimized geometry. The drug receptor interactions of the molecule were studied by molecular docking using auto dock 4.2. [ABSTRACT FROM AUTHOR]

• The antioxidant and thrombolytic potential were evaluated using spectrophotometric and clot lysis methods respectively. • The (1s,15s)bicyclo[13.1.0]hexadecan-2-one compound showed the greatest binding score with 6NGJ (-7.9 kcal/mol) protein. Also, the (1s,15s)bicyclo[13.1.0]hexadecan-2-one compound showed the top binding score with 1A5H (-6.9 kcal/mol) protein. • The ADMET and PASS results depicted that the compounds are non-carcinogenic, have antioxidant, and antiulcerative effects. Corchorus aestuans L. (Malvaceae), a little annual plant, grows in wastelands at low and medium altitudes. It has traditionally been used as an antihistaminic, anti-inflammatory, and antibacterial for chronic cystitis, gonorrhea, and dysuria. Our research aimed to investigate the antioxidant, antimicrobial, and thrombolytic potential of several solvent extracts. Three different solvents were used in the extraction process: methanol, hydro-methanol, and water. Using established qualitative methodologies, phytochemical screening was carried out. Folin-Ciocalteu and aluminum chloride techniques were used to determine the total phenol and flavonoid contents. The antioxidant activity (total antioxidant capacity, DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging, and Fe3+ reducing power) was evaluated using spectrophotometric methods. Besides, clot lysis and disc-diffusion methods were used to assess thrombolytic and antibacterial activity. The GC-MS analysis was also performed to discover prominent phytochemicals. Phytochemical screening revealed the presence of glycosides, alkaloids, flavonoids, phenols, tannins, etc. Among all the extracts, hydro-methanol extract (MACA) possesses the highest total phenol and flavonoid contents (778.2±20.82 mg GAE/g dry extract and 535.44±20.95 mg QE/g dry extract respectively). Similarly, MACA showed the highest total antioxidant capacity (664.31±16.84mg/g equivalent to AA), DPPH scavenging activity (IC 50 : 26.30±2.82 μg/mL), and ferric reducing capacity (EC 50 : 18.58±2.37 μg/mL). Moreover, among the three extracts, MACA showed the highest percentages of clot lysis (40.49 ±1.97 %) and an antibacterial effect against B. subtilis. GC-MS revealed 17 phytoconstituents, whereas (1s,15s) bicyclo [13.1.0] hexadecan-2-one had the greatest binding score with 6NGJ (-7.9 kcal/mol), and 1A5H (-6.9 kcal/mol) proteins. The ADMET studies showed they are non-carcinogenic, and well-absorbed, while PASS prediction and drug-likeness data showed antioxidant, anti-inflammatory, and good oral bioavailability. Therefore, further research will potentiate to discover compounds with antioxidant, thrombolytic, and antibacterial properties, with their mechanism of action. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVDs) are a leading cause of death, and their pathogenesis is commonly attributed to thrombosis. Although existing medications are effective and fast-acting for thrombosis management, they tend to be expensive and cause severe side effects. Plant-based thrombolytic agents are actively sought after as inexpensive and safe alternatives for the treatment and prevention of thrombosis. Red ginger (Zingiber officinale var. rubrum) and white ginger (Zingiber officinale var. officinale) are widely used in foods and beverages and are believed to confer a wide variety of health benefits. Objective: This study aims to elucidate the thrombolytic and fibrinolytic potential of red and white ginger extracts in vitro. Methods: In this study, in vitro analyses were performed using erythrocyte liberation, euglobulin degradation, fibrin degradation, and fibrin zymography assays. The ability of crude enzyme extracts from both red (rgEx) and white ginger (wgEx) to degrade blood clots was analyzed using the erythrocytes liberation assay. Then, the thrombolytic and fibrinolytic activities of rgEx and wgEx were evaluated using euglobulin and fibrin degradation assays, both of which were visualized using Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE). Finally, fibrinolytic enzymes were identified using a fibrin zymography assay. Results: Red and white ginger extracts were found to have strong thrombolytic properties via high total liberated erythrocyte count from the erythrocyte liberation assay. The ginger extract proteases can rapidly degrade euglobulin and fibrin, with their priority order beginning with Aα and Bβ, then γ chains. Fibrin zymography confirmed the presence of several proteases in the red and white ginger extracts. Conclusion: Overall, while red and white ginger crude enzyme extracts have been reported to possess a strong thrombolytic and fibrinolytic potential and are therefore suggested to be good candidates for managing and preventing CVD, further studies such as full enzyme identification and in vivo studies are needed. [ABSTRACT FROM AUTHOR]

Background Pump thrombosis is a serious complication of continuous-flow left ventricular assist device (CF-LVAD) therapy. In this study, we aim to report a novel protocol of an intermittent, low-dose, and slow infusion of tissue plasminogen activator (alteplase). Case summary We treated seven LVAD pump thrombosis events (HeartMate® II and HeartWare) in four patients with a median age of 52 years (31–63), and all were female. The protocol was applied from January 2015 to December 2018, and it consisted of an intermittent, low-dose, and slow infusion of systemic thrombolytic therapy in the intensive care unit. This therapy resulted in successful resolution of pump thrombosis in six out of seven events. Bleeding complication occurred in one patient, which included a ruptured haemorrhagic ovarian cyst and a small cerebellar intra-parenchymal haemorrhage. All patients were discharged home in a stable condition, except one patient who died during hospitalization because of severe sepsis, pump thrombosis with subsequent pump exchange, and multi-organ failure. Discussion A low-dose, prolonged, and systemic thrombolytic infusion protocol is an effective and relatively safe treatment that can lead to a sustained resolution of pump thrombosis with low bleeding complications and failure rates. [ABSTRACT FROM AUTHOR]

Background: There is unclear added benefit of intravenous thrombolysis (IVT) with endovascular thrombectomy (EVT). We performed a cost-effectiveness analysis to assess the cost-effectiveness of comparing EVT with IVT versus EVT alone. Methods: We used a decision tree to examine the short-term costs and outcomes at 90 days after the occurrence of index stroke to compare the cost-effectiveness of EVT alone with EVT plus IVT for patients with stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1-year, 5-year, and 20-year time horizons. We estimated total and incremental cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio. Results: The average costs per patient were estimated to be $47,304, $49,510, $59,770, and $76,561 for EVT-only strategy and $55,482, $57,751, $68,314, and $85,611 for EVT with IVT over 90 days, 1 year, 5 years, and 20 years, respectively. The cost saving of EVT-only strategy was driven by the avoided medication costs of IVT (ranging from $8,178 to $9,050). The additional IVT led to a slight decrease in QALY estimate during the 90-day time horizon (loss of 0.002 QALY), but a small gain over 1-year and 5-year time horizons (0.011 and 0.0636 QALY). At a willingness-to-pay threshold of $50,000 per QALY gained, the probabilities of EVT only being cost-effective were 100%, 100%, and 99.3% over 90-day, 1-year, and 5-year time horizons. Conclusion: Our cost-effectiveness model suggested that EVT only may be cost-effective for patients with acute ischemic stroke secondary to large vessel occlusion. [ABSTRACT FROM AUTHOR]

Background. Over the last three decades, stroke management has witnessed substantial progress, from the introduction of recombinant tissue plasminogen activator (rtPA) in 1995 to the approval of thrombectomy in 2016. Intravenous tissue plasminogen activator (tPA) within 4.5 hours of symptom onset is the standard for eligible acute ischemic stroke patients, dissolving clots and restoring blood flow. Endovascular thrombectomy (EVT) surpasses intravenous thrombolysis for large vessel occlusion cases, typically within 6 to 24 hours based on CT-perfusion criteria. CT perfusion (CTP) provides crucial quantitative data on cerebral blood flow, aiding in ischemia detection, tissue assessment, treatment guidance, and outcome prediction. This case report marks a pivotal moment in Indonesian stroke management, introducing the inaugural use of CTP for diagnostic purposes. By scrutinizing blood flow dynamics and cerebral conditions, CTP augments conventional diagnostics, offering enhanced prognostic value. Case presentation. The case of a 58-year-old male with notable comorbidities exemplifies this successful integration. He presented with sudden left-sided weakness and dysarthria, without accompanying symptoms. Neurological evaluation revealed a Glasgow Coma Scale score of E3M6V5, 7th cranial nerve paresis, and a positive Babinski reflex on the left side. With a National Institute of Health Stroke Scale (NIHSS) score of 10, a head CT scan rules out cerebral hemorrhage, prompting precise thrombolysis at 0.7 mg/kg. Within one hour post-thrombolysis, the NIHSS score improved to 6, ultimately culminating in an NIHSS score of 2 upon discharge. Conclusion. This case underscores the efficacy of acute ischemic stroke management, fortified by the strategic integration of CTP, heralding a new era in Indonesian stroke care.

Thrombolytic agents are used for thrombolytic therapy to dissolve blood clots that form in a blood vessel. All currently used thrombolytic agents have unfavorable shortcomings, such as gastrointestinal bleeding, allergic reactions, and thrombolytic agent resistance, treatment for some of which can be quite expensive. As a result, the search for thrombolytic agents derived from plants is currently taking place. Some plants have been discovered to contain protease enzymes with thrombolytic activity; pharmaceuticals derived from plants are believed to be safer. Jernang rattan (Daemonorops draco) is a plant of the Arecaceae family and is known to produce resin. Jernang rattan resin is also known to have antioxidant, antiseptic, antitumor, antimicrobial, and cytotoxic activity, but very limited information on proteolytic activity of the protease from this plant. This research aims to isolate proteases from the leaves and fruit flesh of the rattan jernang plant (D. draco) and to investigate the proteolytic activity of the isolated proteases. The protease was isolated from the leaves and the fruit flesh, and then partially purified by ammonium sulfate precipitation. The radial caseinolytic assay showed that protease in a 60% ammonium sulfate fraction gave a clear zone, with diameters of 1.4 cm and 1.8 cm for the protease isolated from leaves and fruit flesh, respectively. A Folin‐Ciocalteau assay showed that the enzymes isolated were able to hydrolyze casein and release L‐tyrosine, with activity of 0.158 U/mL and 0.174 U/mL for the protease from the leaves and fruit flesh, respectively. A fibrinogenolytic assay showed that the protease from the fruit flesh hydrolyzed the A‐α, B‐β and the γ chain of human fibrinogen, while the protease from the leaves hydrolyzed the A‐α and γ chain. Both proteases were inhibited by 56% by phenylmethylsulfonyl fluoride (PMSF), indicating that the enzymes are serine proteases. Based on the assay results obtained, it can be concluded that proteases isolated from the leaves and fruit flesh have potential as thrombolytic proteases.

Introduction: Natural plant-based medicines have gained popularity recently as a major source of inventive, risk-free, and more potent secondary bioactive compounds with medicinal potential. Catharanthus ovalis is a perennial shrub containing various indole alkaloids cultivated extensively for local medical purposes.Methods: This research is conducted to identify the phytocompounds present in the leaves of C. ovalis and its central and peripheral analgesic, thrombolytic, and membrane-stabilizing activities through tail immersion, acetic acid-induced writhing, human blood clot lysis, and erythrocyte lysis by heat and hypotonic solution methods, respectively.Results and discussion: A total of 39 compounds were identified using GC–MS/MS techniques, including hexadecanoic acid, methyl ester (56.749%), methyl stearate (29.782%), carvacrol and its TBDMS derivative (12.586%), and 9-octadecenoic acid, methyl ester, (E)-] (9.297%) presented in high quantity. The highest tail immersion latency was observed for the 600 mg/kg extract of C. ovalis crude extract. Both 400 and 600 mg/kg doses of C. ovalis crude extract exhibited prominent peripheral analgesic activity. The maximum thrombolytic effect was observed by DCM soluble fraction extract by inhibiting 54.87% of the clot. However, the aqueous-soluble fraction of this extract manifested an excellent membrane-stabilizing effect by showing 73.98% and 87.51% hemolysis against heat- and hypotonic-induced hemolysis, respectively. Some of the compounds were identified as active agents against different receptors related to these diseases, which supported the findings of in vitro and in vivo tests.Conclusion: Further investigation needs to be conducted to specify and identify the exact mechanism of action of these compounds.

Introduction: A myocardial infarction (MI), commonly known as a heart attack, is the result of a sudden interruption in the blood flow to the heart muscle. This is frequently caused by a blood clot forming within the coronary arteries. Acute myocardial infarction (AMI) is a major health hazard that causes over a million deaths annually in the US and affects up to 3 million people globally. Thrombolytic therapy, such streptokinase, is used to break up blood clots and improve blood flow, which stops ischemia injury. Injectable streptokinase is used to activate plasminogen in a nonenzymatic manner. Material And Method: This study examined thrombolytic outcomes in 120 patients with ST elevation myocardial infarction (STEMI) using a prospective interventional trial design. Patients were grouped according to gender and diabetes status. A thorough statistical analysis was carried out, looking at the relationship between gender and diabetes status and thrombolytic outcomes. Measurements such as glucose levels, ECG results, and random blood sugar were examined. Result: There were notable differences in ST segment resolution between MI patients with diabetes and those without. Of the 70 diabetic MI patients, 61.42% had failed thrombolysis (less than 30% ST resolution), whereas 21.42% had successfully completed thrombolysis (more than 70% resolution) (p=0.003). Compared to diabetics, non-diabetic MI patients (n=50) had a greater success rate (44%) and a higher percentage of failed thrombolysis (24%; p=0.049). Anterior wall MI was more common in both groups, followed by inferior wall MI, while anteroseptal MI was less common. Men with diabetes (n = 45) demonstrated 23 failed, 10 partial, and 12 effective resolutions; women with diabetes (n = 25) demonstrated 11 failed, 9 partial, and 5 successful resolutions. Non-diabetic females (n=25) had only two instances of unsuccessful resolution, compared to three among non-diabetic males (n=25). Conclusion: When comparing the thrombolytic effects of streptokinase, patients with diabetes had a higher incidence of unsuccessful thrombolysis (less than 30% ST resolution) than their non-diabetic counterparts. On the other hand, non-diabetic STEMI patients are more likely to have effective thrombolysis (>70% ST resolution). This highlights the effect of type 2 diabetes on the results of thrombolysis. Given the documented difficulties in establishing successful thrombolysis in this subgroup, percutaneous coronary intervention may therefore be preferred to thrombolysis in diabetic STEMI cases. [ABSTRACT FROM AUTHOR]

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Selenium nanoparticles (SeNPs) have gained wide importance in the scientific community and have emerged as an optimistic therapeutic carrier agent for targeted drug delivery. In the present study, the effectiveness of nano selenium conjugated with Morin (Ba-SeNp-Mo) produced from endophytic bacteria Bacillus endophyticus reported in our earlier research was tested against various Gram-positive, Gram-negative bacterial pathogens and fungal pathogens that showed good zone of inhibition against all selected pathogens. Antioxidant activities of these NPs were studied by 1, 1-diphenyl-2- picrylhydrazyl (DPPH), 2,2′-Azino-bis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS), hydrogen peroxide (H2O2), superoxide (O2−), and nitric oxide (NO) radical scavenging assays that exhibited dose-dependent free radical scavenging activity with IC50 values 6.92 ± 1.0, 16.85 ± 1.39, 31.60 ± 1.36, 18.87 ± 1.46, and 6.95 ± 1.27 μg/mL. The efficiency of DNA cleavage and thrombolytic activity of Ba-SeNp-Mo were also studied. The antiproliferative effect of Ba-SeNp-Mo was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in COLON-26 cell lines that resulted in IC50 value of 63.11 μg/mL. Further increased intracellular reactive oxygen species (ROS) levels up to 2.03 and significant early, late and necrotic cells were also observed in AO/EtBr assay. CASPASE 3 expression was upregulated to 1.22 (40 μg/mL) and 1.85 (80 μg/mL) fold. Thus, the current investigation suggested that the Ba-SeNp-Mo has offered remarkable pharmacological activity. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Prompt diagnosis and management of massive pulmonary embolism after bariatric surgery is crucial, but thrombolytic therapy may increase the risk of complications such as anastomotic leakage and bleeding. Individualized management is needed. [ABSTRACT FROM AUTHOR]

Background: The intraoperative use of thrombolytic agents, such as urokinase, is an established adjunct technique in free flap salvage. However, choice of agent, technique of administration and dosage varies across reconstructive units, with no consensus on optimal protocol. Methods: A retrospective review was performed of free flaps requiring operative exploration and salvage at our institution between July 2016 and June 2022. Flaps with persistent poor venous outflow despite standard salvage measures received urokinase thrombolytic therapy. A literature review was also performed to identify existing urokinase administration protocols, including indication and technique of administration. A search of PubMed and Embase databases was performed to identify relevant articles published between 1982 and 2022. Results: 28 flaps required takeback to theatre for exploration and attempted salvage, with an overall salvage success rate of 71%. Urokinase was used in 8 cases when the flap did not respond intraoperatively to standard salvage procedures, with salvage success of 38%. For the literature review, 155 articles met our search criteria. 10 articles were suitable to be reviewed. Due to study heterogeneity and small case numbers, statistical analysis was not possible. A summative review of findings and outcomes was instead performed to compare with our own experience. Conclusions: There is lack of uniformity in urokinase administration protocols across reconstructive units. We present a step-by step protocol for the use of intraoperative urokinase in free flap salvage that is easy to understand and follow. Standardisation of administration protocol and larger case series are required to determine the true efficacy and utility of urokinase. Level of evidence: Level IV, Therapeutic. [ABSTRACT FROM AUTHOR]

Background. Over the last three decades, stroke management has witnessed substantial progress, from the introduction of recombinant tissue plasminogen activator (rtPA) in 1995 to the approval of thrombectomy in 2016. Intravenous tissue plasminogen activator (tPA) within 4.5 hours of symptom onset is the standard for eligible acute ischemic stroke patients, dissolving clots and restoring blood flow. Endovascular thrombectomy (EVT) surpasses intravenous thrombolysis for large vessel occlusion cases, typically within 6 to 24 hours based on CT-perfusion criteria. CT perfusion (CTP) provides crucial quantitative data on cerebral blood flow, aiding in ischemia detection, tissue assessment, treatment guidance, and outcome prediction. This case report marks a pivotal moment in Indonesian stroke management, introducing the inaugural use of CTP for diagnostic purposes. By scrutinizing blood flow dynamics and cerebral conditions, CTP augments conventional diagnostics, offering enhanced prognostic value. Case presentation. The case of a 58-year-old male with notable comorbidities exemplifies this successful integration. He presented with sudden left-sided weakness and dysarthria, without accompanying symptoms. Neurological evaluation revealed a Glasgow Coma Scale score of E3M6V5, 7th cranial nerve paresis, and a positive Babinski reflex on the left side. With a National Institute of Health Stroke Scale (NIHSS) score of 10, a head CT scan rules out cerebral hemorrhage, prompting precise thrombolysis at 0.7 mg/kg. Within one hour post-thrombolysis, the NIHSS score improved to 6, ultimately culminating in an NIHSS score of 2 upon discharge. Conclusion. This case underscores the efficacy of acute ischemic stroke management, fortified by the strategic integration of CTP, heralding a new era in Indonesian stroke care. [ABSTRACT FROM AUTHOR]

Background and Aims: The study aimed to evaluate the pharmacological properties of methanolic extracts of leaves and barks of Woodfordia fruticosa (L.) Kurz (family: Lythraceae) focusing on antioxidant, thrombolytic, anti‐inflammatory, antibacterial, analgesic, and antidiarrheal effects. Methods: 1,1‐Diphenyl‐2‐picrylhydrazyl (DPPH) free radical scavenging assay, clot lysis, disc diffusion, and membrane stabilizing methods were employed to assess in vitro antioxidant, thrombolytic, antibacterial, and anti‐inflammatory properties of the leaf and bark methanolic extracts (ME) of W. fruticosa and different organic solvents, that is, petroleum ether (PE), dichloromethane (DCM), chloroform (CL), and aqueous (AQ) fractions. In addition, in vivo central and peripheral analgesic and antidiarrheal activities of both crude extracts were evaluated at two doses (200 and 400 mg/kg of body weight [bw]). Results: All the extracts and fractions showed promising antioxidant properties by scavenging DDPH free radicals with IC50 of 6.11–20.79 μg/mL. AQ fraction (41.24%) of leaves and ME (44.90%) of bark exerted notable in vitro thrombolytic activity. The CL fraction of leaves and AQ fraction of the bark showed 43.16% and 45.37% inhibition of RBC hemolysis, respectively, compared to the inhibition of RBC hemolysis by aspirin in a hypotonic‐induced membrane stabilizing assay. Besides, both extracts were observed to provide significant (p < 0.001) central and peripheral analgesic responses at both doses of 200 and 400 mg/kg bw. Furthermore, both doses of bark extract (p < 0.001) and the 400 mg/kg bw of leaf extract (p < 0.05) were observed to possess statistically significant antidiarrheal activity. Additionally, in an in vivo acute toxicity investigation, both extracts had a median lethal dose (LD50) greater than 5000 mg/kg bw, indicating their safety level. Conclusion: The current study proves the ethnomedicinal uses of W. fruticosa; however, further studies are required for phytochemical screening to isolate the responsible bioactive compounds and discover the lead molecules from the plant species. [ABSTRACT FROM AUTHOR]

Piperazine is a privileged moiety that is a structural part of many clinical drugs. Piperazine-based scaffolds have attracted the attention of pharmaceutical and medicinal scientists to develop novel, efficient therapeutic agents owing to their significant and promising biological profile. In the current study, an ecofriendly ultrasonic-assisted synthetic approach was applied to achieve a novel series of 1-tosyl piperazine dithiocarbamate acetamide hybrids 4a–4j, which was evaluated for in vitro tyrosinase inhibition and thrombolytic and hemolytic cytotoxic activities. Among all the piperazine-based dithiocarbamate acetamide target molecules 4a–4j, the structural analogs 4d displayed excellent tyrosinase inhibition efficacy (IC50 = 6.88 ± 0.11 µM) which was better than the reference standard drugs kojic acid (30.34 ± 0.75 µM) and ascorbic acid (11.5 ± 1.00 µM), respectively, which was further confirmed by in silico induced-fit docking (IFD) simulation Good tyrosinase activities were exhibited by 4g (IC50 = 7.24 ± 0.15 µM), 4b (IC50 = 8.01 ± 0.11 µM) and 4c (IC50 = 8.1 ± 0.30 µM) dithiocarbamate acetamides, which were also better tyrosinase inhibitors than the reference drugs but were less active than the 4d structural hybrid. All the derivatives are less toxic, having values in the 0.29 ± 0.01% to 15.6 ± 0.5% range. The scaffold 4b demonstrated better hemolytic potential (0.29 ± 0.01%), while a remarkably high thrombolytic chemotherapeutic potential was displayed by analog 4e (67.3 ± 0.2%). [ABSTRACT FROM AUTHOR]

Mirabilis jalapa L. belongs to Nyctaginaceae family is an ornamental plant and domestically known as Sandhamaloti in Bangladesh. In this report we evaluated phenol and flavonoid content of cold methanol extractives of flower of M. jalapa and their role in antioxidant, antibacterial, cytotoxic and thrombolytic potentials. This study utilized HPLC to identify qualitative phenolic and flavonoid compounds. Gallic acid and Kaempferol were employed as standards for phenolic and flavonoid identification, respectively. Consequently, evaluating the overall phenolic and flavonoid content in the plant extract was considered a logical step. Flower of M. jalapa is an abundant source of phenols and flavonoids. The antioxidant activities in the phosphomolybdenum assay are differed in distinct extractives and have been found as 334.78 ± 0.62, 142.53 ± 0.51, 398.04 ± 0.81, 470.29 ± 0.55 and 480.90 ± 0.59 mg of ascorbic acid equivalent per gm of crude methanol extract (MSF), petroleum ether fraction (PSF), carbon tetrachloride fraction (CTF), chloroform fraction (CSF) and ethyl acetate fraction (ESF), respectively. The IC50 values for DPPH radical scavenging have been evaluated to be 13.70 ± 0.32, 49.05 ± 0.47, 6.76 ± 0.22, 9.30 ± 0.41 and 6.94 ± 0.31 μg/mL for MSF, PSF, CTF, CSF and ESF, respectively. The cytotoxicity was evaluated against brine shrimp lethality bioassay and LC50 values of MSF, PSF, CTF, CSF and ESF have been found 11.83 ± 0.32, 35.50 ± 0.54, 5.00 ± 0.18, 11.30 ± 0.30 and 4.61 ± 0.15 μg/mL, respectively in comparison to a standard vincristine sulphate 2.50 ± 0.11 μg/mL. Plant polyphenols and flavonoids having antioxidant properties exhibit potential antibacterial activity and our results revealed that the entire tested fractions of vegetation of M. jalapa exhibit potential antibacterial activity. On this observation, the thrombolytic activity, is the first strive in M. jalapa to investigate for more modern thrombolytic and its ethyl acetate fraction was shown to substantial (53.81 ± 0.52%) thrombolysis property. A high correlation was observed between antioxidant, cytotoxicity, thrombolytic and antibacterial activity with polyphenol and flavonoid contents (r2 = 0.903 to 0.996, p

Key Clinical Message Prompt diagnosis and management of massive pulmonary embolism after bariatric surgery is crucial, but thrombolytic therapy may increase the risk of complications such as anastomotic leakage and bleeding. Individualized management is needed.

Abstract Background and Aims The study aimed to evaluate the pharmacological properties of methanolic extracts of leaves and barks of Woodfordia fruticosa (L.) Kurz (family: Lythraceae) focusing on antioxidant, thrombolytic, anti‐inflammatory, antibacterial, analgesic, and antidiarrheal effects. Methods 1,1‐Diphenyl‐2‐picrylhydrazyl (DPPH) free radical scavenging assay, clot lysis, disc diffusion, and membrane stabilizing methods were employed to assess in vitro antioxidant, thrombolytic, antibacterial, and anti‐inflammatory properties of the leaf and bark methanolic extracts (ME) of W. fruticosa and different organic solvents, that is, petroleum ether (PE), dichloromethane (DCM), chloroform (CL), and aqueous (AQ) fractions. In addition, in vivo central and peripheral analgesic and antidiarrheal activities of both crude extracts were evaluated at two doses (200 and 400 mg/kg of body weight [bw]). Results All the extracts and fractions showed promising antioxidant properties by scavenging DDPH free radicals with IC50 of 6.11–20.79 μg/mL. AQ fraction (41.24%) of leaves and ME (44.90%) of bark exerted notable in vitro thrombolytic activity. The CL fraction of leaves and AQ fraction of the bark showed 43.16% and 45.37% inhibition of RBC hemolysis, respectively, compared to the inhibition of RBC hemolysis by aspirin in a hypotonic‐induced membrane stabilizing assay. Besides, both extracts were observed to provide significant (p

Abstract The hyper-coagulopathy nature of COVID-19 is a prevalent consequence among patients. Free-floating right atrial thrombi are a relatively rare finding and the optimal therapy is a therapeutic dilemma. We present a 37-year-old woman with acute dyspnea and fatigue. Several ground glass opacities were shown on computed tomography of chest that further proved to be associated with severe COVID-19 disease. A transthoracic echocardiography revealed a mobile right atrial mass with bilateral pulmonary embolism. She was considered high risk for surgical therapy by cardiovascular surgeons. She was then started on anticoagulation therapy for 5 days however the size regression of the thrombus remained unchanged. A regimen of low dose (24 mg) ultra-slow (24 h) intravenous infusion of alteplase, without bolus was initiated. Following the third day of thrombolytic therapy, the control echocardiography demonstrated complete resolution of the thrombus. Prolonged infusion of low dose fibrinolytics can be an alternative treatment to surgery for right heart thrombi.

The objective of the current study was to examine the phytochemical and in vitro thrombolytic, anti-arthritic, anthelmintic, and insecticidal effects of Trewia nudiflora (TN) methanolic leaf extract with its methanol (MTN), chloroform (CTN), and ethyl acetate (ETN) fractions. Pheretima posthuma and Tribolium castaneum were employed for evaluating the antihelmintic and insecticidal properties, respectively. All the tested extracts showed the presence of copious potential constituents in phytochemical analysis. Among all extracts, MTN extract exhibited the utmost clot lysis (35.95 ± 4.81%) property compared to standard streptokinase (SK) (53.77 ± 7.52%). All samples displayed striking protein denaturation activity in a dose-dependent manner (100–500 µg/mL), where the highest inhibition was observed for MTN (67.26 ± 6.39% at 500 µg/mL). Each extract demonstrated considerable anthelmintic activity at 25–75 mg/mL dose ranges. ETN showed the strongest anthelmintic activity at the highest dose. Among all samples, the CTN extract displayed the utmost mortality rate (77.22%) in the insecticidal test. The results of the study suggest that T. nudiflora leaf extracts may have potential against thrombosis, arthritis, helminths, and insects, which warrants the necessity of extensive isolation and identification of bioactive compounds to develop newer effective drugs upon preclinical and clinical investigations.

Background: Thrombolytic agents such as tissue plasminogen activator (tPA) are the only drug class approved to treat ischemic stroke and are usually administered within 4.5 h. However, only ~20% of ischemic stroke patients are eligible to receive the therapy. We previously demonstrated that early intravenous administration of human amnion epithelial cells (hAECs) can limit brain inflammation and infarct growth in experimental stroke. Here, we have tested whether hAECs exert cerebroprotective effects in combination with tPA in mice. Methods: Male C57Bl/6 mice were subjected to middle cerebral artery occlusion for 60 min followed by reperfusion. Immediately following reperfusion, vehicle (saline, n = 31) or tPA (10 mg/kg; n = 73) was administered intravenously. After 30 min of reperfusion, tPA-treated mice were injected intravenously with either hAECs (1×106; n = 32) or vehicle (2% human serum albumin; n = 41). A further 15 sham-operated mice were treated with vehicle (n = 7) or tPA + vehicle (n = 8). Mice were designated to be euthanised at 3, 6 or 24 h post-stroke (n = 21, 31, and 52, respectively), and brains were collected to assess infarct volume, blood-brain barrier (BBB) disruption, intracerebral bleeding and inflammatory cell content. Results: There was no mortality within 6 h of stroke onset, but a high mortality occurred in tPA + saline-treated mice between 6 h and 24 h post-stroke in comparison to mice treated with tPA + hAECs (61% vs. 27%, p = 0.04). No mortality occurred within 24 h of sham surgery in mice treated with tPA + vehicle. We focused on early infarct expansion within 6 h of stroke and found that infarction was ~50% larger in tPA + saline-than in vehicle-treated mice (23 ± 3 mm³ vs. 15 ± 2 mm³, p = 0.02) but not in mice receiving tPA + hAECs (13 ± 2 mm3, p < 0.01 vs. tPA + saline) in which intracerebral hAECs were detected. Similar to the profiles of infarct expansion, BBB disruption and intracerebral bleeding in tPA + saline-treated mice at 6 h was 50-60% greater than in vehicle-treated controls (2.6 ± 0.5 vs. 1.6 ± 0.2, p = 0.05) but not after tPA + hAECs treatment (1.7 ± 0.2, p = 0.10 vs. tPA + saline). No differences in inflammatory cell content were detected between treatment groups. Conclusion: When administered following tPA in acute stroke, hAECs improve safety and attenuate infarct growth in association with less BBB disruption and lower 24 h mortality. [ABSTRACT FROM AUTHOR]

Background: Tenecteplase is a genetically engineered fibrinolytic with growing interest in the treatment of acute ischemic stroke. Compared to alteplase, tenecteplase is effective for neurologic improvement following ischemic stroke in patients with large vessel occlusions who are eligible for thrombectomy and for mild ischemic strokes with National Institutes of Health Stroke Scale of 0 to 5. Objective: The purpose of this study is to determine if safety outcomes are different in patients receiving tenecteplase and alteplase for acute ischemic stroke. Methods: This retrospective cohort reviewed all patients who received alteplase or tenecteplase from January 2019 to December 2020. Patients admitted before April 28, 2020, received alteplase intravenous bolus over 1 minute followed by an infusion over 1 hour, for a total of 0.9 mg/kg. Patients admitted after this date received tenecteplase 0.25 mg/kg as an intravenous bolus over 5 to 10 seconds. Any patient transferring from an outside facility was excluded. The primary outcome was major bleeding. Results: There was no significant difference in major bleeding between alteplase and tenecteplase (40 [18%] vs 21 [18.1%], P = 0.985). There was no significant difference in all-cause inpatient mortality for alteplase versus tenecteplase (10 [5%] vs 5 [4%], P = 0.934) or in adverse events between the groups (22 [9%] vs 14 [12%], P = 0.541) for alteplase and tenecteplase, respectively. Conclusions and Relevance: Tenecteplase had similar rates of major bleeding versus alteplase and may be a reasonable alternative in the treatment of acute ischemic stroke. [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.

BackgroundThrombolytic agents such as tissue plasminogen activator (tPA) are the only drug class approved to treat ischemic stroke and are usually administered within 4.5 h. However, only ~20% of ischemic stroke patients are eligible to receive the therapy. We previously demonstrated that early intravenous administration of human amnion epithelial cells (hAECs) can limit brain inflammation and infarct growth in experimental stroke. Here, we have tested whether hAECs exert cerebroprotective effects in combination with tPA in mice.MethodsMale C57Bl/6 mice were subjected to middle cerebral artery occlusion for 60 min followed by reperfusion. Immediately following reperfusion, vehicle (saline, n = 31) or tPA (10 mg/kg; n = 73) was administered intravenously. After 30 min of reperfusion, tPA-treated mice were injected intravenously with either hAECs (1×106; n = 32) or vehicle (2% human serum albumin; n = 41). A further 15 sham-operated mice were treated with vehicle (n = 7) or tPA + vehicle (n = 8). Mice were designated to be euthanised at 3, 6 or 24 h post-stroke (n = 21, 31, and 52, respectively), and brains were collected to assess infarct volume, blood–brain barrier (BBB) disruption, intracerebral bleeding and inflammatory cell content.ResultsThere was no mortality within 6 h of stroke onset, but a high mortality occurred in tPA + saline-treated mice between 6 h and 24 h post-stroke in comparison to mice treated with tPA + hAECs (61% vs. 27%, p = 0.04). No mortality occurred within 24 h of sham surgery in mice treated with tPA + vehicle. We focused on early infarct expansion within 6 h of stroke and found that infarction was ~50% larger in tPA + saline- than in vehicle-treated mice (23 ± 3 mm3 vs. 15 ± 2 mm3, p = 0.02) but not in mice receiving tPA + hAECs (13 ± 2 mm3, p

The most concerning adverse effects of thrombolytic agents are major bleeding and intracranial hemorrhage due to their short half-life, low fibrin specificity, and high dosage. To alleviate bleeding side effects during thrombolytic therapy which would bring about the risk of aggravation, we try to find a novel biodegradable delivery nanosystem to carry drugs to target the thrombus, reduce the dosage of the drug, and system side effects. A novel urokinase/poly-α, β-d, l-aspartyl-Arg-Gly-Asp-Ser complex (UK/PD-RGDS) was synthesized and simply prepared. Its thrombolytic potency was assayed by the bubble-rising method and in vitro thrombolytic activity by the thrombus clot lysis assay separately. The in vivo thrombolytic activity and bleeding complication were evaluated by a rat model of carotid arteriovenous bypass thrombolysis. The thrombolytic potency (1288.19 ± 155.20 U/mg) of the UK/PD-RGDS complex nano-globule (18–130 nm) was 1.3 times that of commercial UK (966.77 ± 148.08 U/mg). In vivo, the UK/PD-RGDS complex (2000 IU/kg) could reduce the dose of UK by 90% while achieving the equivalent thrombolysis effect as the free UK (20,000 IU/kg). Additionally, the UK/PD-RGDS complex decreased the tail bleeding time compared with UK. The organ distribution of the FITC-UK/PD-RGDS complex was explored in the rat model. The UK/PD-RGDS complex could provide a promising platform to enhance thrombolytic efficacy significantly and reduce the major bleeding degree. [ABSTRACT FROM AUTHOR]

The hyper-coagulopathy nature of COVID-19 is a prevalent consequence among patients. Free-floating right atrial thrombi are a relatively rare finding and the optimal therapy is a therapeutic dilemma. We present a 37-year-old woman with acute dyspnea and fatigue. Several ground glass opacities were shown on computed tomography of chest that further proved to be associated with severe COVID-19 disease. A transthoracic echocardiography revealed a mobile right atrial mass with bilateral pulmonary embolism. She was considered high risk for surgical therapy by cardiovascular surgeons. She was then started on anticoagulation therapy for 5 days however the size regression of the thrombus remained unchanged. A regimen of low dose (24 mg) ultra-slow (24 h) intravenous infusion of alteplase, without bolus was initiated. Following the third day of thrombolytic therapy, the control echocardiography demonstrated complete resolution of the thrombus. Prolonged infusion of low dose fibrinolytics can be an alternative treatment to surgery for right heart thrombi. [ABSTRACT FROM AUTHOR]

Background & Objective: Acute myocardial infarction (MI) is caused due to coronary artery occlusion and divided into two forms of ST-elevation (STEMI) and non-ST-elevation (NSTEMI) myocardial infarction. This study aimed to determine the success rate of treatment with primary PCI (percutaneous coronary intervention) versus thrombolysis in the establishment of perfusion and to evaluate the short-term complications caused by each method. Materials & Methods: In this prospective cohort study, 90 patients were selected for primary PCI treatment and 90 patients for thrombolytic treatment. Clinical data and basic demographic characteristics of the patients and cardiovascular risk factors were recorded. The success rate of coronary reperfusion by primary PCI and thrombolytic therapy was then determined by angiography and 90-minute ECG with resolution or improvement of chest pain. All patients were examined for any serious complications such as cerebrovascular accidents, shock, and heart failure for 30 days after treatment. Data were analyzed using SPSS ver. 20. Results: In the primary PCI group, 75.6% of the patients were males, and 24.4% were females, but in the thrombolytic group, 76.6% and 23.3% of the cases were males and females, respectively. The mean door-to-balloon time for PCI was 63.60 ± 23.92 and was 53.70 ±21.52 min in the thrombolytic group. Thrombolysis in myocardial infarction (TIMI) flow grade III and TIMI-II were the most frequent in primary PCI and thrombolytic groups, respectively. The odds ratio (OD) of mechanical MI and major arrhythmia in patients received the primary PCI compared to those received thrombolytic therapy was 0.24 and 0.66, respectively. Also, the OD of mortality in the primary PCI group was 2.12. Conclusion: Our findings suggest that in STEMI patients, the chances of short term complications such as post-MI mechanical complications, major arrhythmia, and bleeding requiring blood transfusion were lower in patients who were treated with primary PCI than those who received thrombolytic treatment. Also, the average hospitalization in CCU and hospital in the primary PCI group was lower than the thrombolytic group. [ABSTRACT FROM AUTHOR]

Direct-acting oral anticoagulants (DOACs) are prescribed in the treatment of venous thromboembolism, including pulmonary embolism (PE). Evidence is limited regarding the outcomes and optimal timing of DOACs in patients with intermediate- or high-risk PE treated with thrombolysis. We conducted a retrospective analysis of outcomes among patients with intermediate- and high-risk PE who received thrombolysis, by choice of long-term anticoagulant agent. Outcomes of interest included hospital length of stay (LOS), intensive care unit LOS, bleeding, stroke, readmission, and mortality. Descriptive statistics were used to examine characteristics and outcomes among patients, by anticoagulation group. Patients receiving a DOAC (n = 53) had shorter hospital LOS compared to those in warfarin (n = 39) and enoxaparin (n = 10) groups (mean LOS 3.6, 6.3 and 4.5 days, respectively; P<.0001). This single institution retrospective study suggests DOAC initiation <48 h from thrombolysis may result in shorter hospital LOS compared to DOAC initiation ≥48 h (P<.0001). Further larger studies with more robust research methodology are needed to address this important clinical question. [ABSTRACT FROM AUTHOR]

Background: Acute ischemic stroke is a leading cause of death and long-term disability. To improve patient outcomes, timely restoration of blood flow to the ischemic brain tissue is vital. One reperfusion strategy includes the administration of thrombolytics. Historically, alteplase has been the thrombolytic of choice for acute ischemic stroke; however, given recent safety and efficacy data, tenecteplase has gained popularity due to its optimal pharmacokinetic profile. Objectives: This study compares outcomes between adult patients with acute ischemic stroke who received tenecteplase as the preferred thrombolytic versus alteplase. Methods: This was a single center, retrospective cohort study that included adult patients who received intravenous thrombolytic therapy, either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg, for acute ischemic stroke from May 2021 to December 2023. The primary outcome was door-to-needle time. Secondary safety outcomes included the incidence of symptomatic intracerebral hemorrhage (ICH), any ICH on 24-hour follow-up imaging, major extracranial bleeding, and angioedema. Secondary efficacy outcomes included discharge with a favorable neurological outcome, discharge disposition, ICU length of stay, and overall length of stay. Secondary stroke metric times evaluated include door-to-computed tomography (CT) time, CT-to-needle time, neurologist notification-to-needle time, and thrombolytic decision-to-needle time. Results: Fifty patients were included in the alteplase group and 50 patients were included in the tenecteplase group. The primary outcome, door-to-needle time, was significantly shorter in the tenecteplase group (36 vs 30 minutes, P = .006). There were no statistically significant differences found in the secondary safety and efficacy outcomes. Patients who received tenecteplase experienced significantly faster CT-to-needle times (17 vs 11 minutes, P = .006), neurologist notification-to-needle times (32 vs 25 minutes, P = .001), and thrombolytic decision-to-needle times (9 vs 5 minutes, P < .001). Conclusions: In this retrospective, observational study, there was a statistically significant decrease in door-to-needle time with tenecteplase compared to alteplase. No significant differences in secondary safety and efficacy outcomes were observed. [ABSTRACT FROM AUTHOR]

Piperazine is a privileged moiety that is a structural part of many clinical drugs. Piperazine-based scaffolds have attracted the attention of pharmaceutical and medicinal scientists to develop novel, efficient therapeutic agents owing to their significant and promising biological profile. In the current study, an ecofriendly ultrasonic-assisted synthetic approach was applied to achieve a novel series of 1-tosyl piperazine dithiocarbamate acetamide hybrids 4a–4j, which was evaluated for in vitro tyrosinase inhibition and thrombolytic and hemolytic cytotoxic activities. Among all the piperazine-based dithiocarbamate acetamide target molecules 4a–4j, the structural analogs 4d displayed excellent tyrosinase inhibition efficacy (IC50 = 6.88 ± 0.11 µM) which was better than the reference standard drugs kojic acid (30.34 ± 0.75 µM) and ascorbic acid (11.5 ± 1.00 µM), respectively, which was further confirmed by in silico induced-fit docking (IFD) simulation Good tyrosinase activities were exhibited by 4g (IC50 = 7.24 ± 0.15 µM), 4b (IC50 = 8.01 ± 0.11 µM) and 4c (IC50 = 8.1 ± 0.30 µM) dithiocarbamate acetamides, which were also better tyrosinase inhibitors than the reference drugs but were less active than the 4d structural hybrid. All the derivatives are less toxic, having values in the 0.29 ± 0.01% to 15.6 ± 0.5% range. The scaffold 4b demonstrated better hemolytic potential (0.29 ± 0.01%), while a remarkably high thrombolytic chemotherapeutic potential was displayed by analog 4e (67.3 ± 0.2%).