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Background: Ischemic heart disease and myocardial infarction are the most common causes of death in the world, and nurses play a key role in the management of these patients. Adequate attitude of health care workers towards the management of patients with acute myocardial infarction using thrombolytic agents is very important and this issue is part of patients' rights. Objectives: The present study was conducted with the aim of study investigate the attitude of nurses and doctors regarding the management of patients with acute myocardial infarction using thrombolytic agents in the teaching hospitals of Babylon, Iraq in 2022. Methodology: In this comparative study, 103 nurses and 13 doctors were selected in 2022 by available sampling method the type of sample was purposive and was conducted on nurses and doctors working in cardiac and coronary resuscitation units in Babylon Specialized Hospitals. Information was collected using two questionnaires including demographic questionnaire and attitude measurement questionnaire the attitudes questionnaire contained parts that included nurses and doctors, and a section specific to nurses only. Results: Among the studied nurses, the largest number were university nurses (36.9% bachelor, 8.7% master). (89.3%) of the nurses had work experience in the coronary care department and (73.8%) of them were currently working in the coronary care department. (78.6%) worked in the morning shift. (76.7%) of the nurses did not have a history of passing the training course in the coronary care department. (54.4%) of the nurses have a diploma and only (2.9%) of them have completed an academic course. The score of doctor’s attitude about the management of patients with acute myocardial infarction using thrombolytic agents was in the range of 68 to 98 with a mean and standard deviation of 83.62 ± 9.62. Based on the results of the independent t-test, there was no significant difference between nurses and doctors regarding the management of patients with acute myocardial infarction using thrombolytic agents (p=0.210). Conclusion: The study concludes that both nurses and doctors in Babylon Teaching Hospitals show a positive attitude towards managing acute myocardial infarction patients using thrombolytic agents. Despite variations in experience and training, both groups are prepared to provide effective care for these patients. The findings suggest a readiness within the medical staff to handle cases of AMI with thrombolytic therapy, highlighting the importance of continued education and training in coronary care management. [ABSTRACT FROM AUTHOR]

The article presents the findings of a study that examined the antithrombotic potential of a protease produced by Bacillus thuringiensis HSFI-12. The study used rats as a model and induced thrombosis in their tails. The results showed that the protease concentrate exhibited antithrombotic effects and improved coagulation parameters. The study suggests that the protease has potential as a therapeutic agent for thrombosis, but further testing is required before it can be used commercially. [Extracted from the article]

Background: The mechanical properties of therapeutic ultrasound (US) have attracted scientific interest for thrombolysis enhancement in combination with thrombolytic agents and microbubbles (MBs). The aim of the study was to develop an in vitro model to observe how the effects of sonothrombolysis change in the case where a tissue-mimicking material (TMM) is placed in the path of the US beam before the clot. Methods: Fully retracted blood clots were prepared and pulse sonicated for 1 h under various conditions. The system was in a state of real circulating flow with a branch of an open bypass and an occluded tube containing a blood clot, thus mimicking the case of ischemic stroke. The effectiveness of thrombolysis was quantified in milligrams of clots removed. An agar-based TMM was developed around the occluded tube. Results: The clot breakdown in a TMM was found to be more pronounced than in water, presumably due to the retention of the acoustic field. A higher level of acoustic power was required to initiate clot lysis (>76 W acoustic power) using only focused US (FUS). The greatest thrombolysis enhancement was observed with the largest chosen pulse duration (PD) and the use of MBs (150 mg clot mass lysis). The synergistic effect of FUS in combination with MBs on the enzymatic fibrinolysis enhanced thrombolysis efficacy by 260% compared to thrombolysis induced using only FUS. A reduction in the degree of clot lysis was detected due to the attenuation factor of the intervening material (30 mg at 1 and 4 ms PD). Conclusion: In vitro thrombolytic models including a TMM can provide a more realistic evaluation of new thrombolytic protocols. However, higher acoustic power should be considered to compensate for the attenuation factor. The rate of clot lysis is slow and the clinical use of this method will be challenging. [ABSTRACT FROM AUTHOR]

Background: The mechanical properties of therapeutic ultrasound (US) have attracted scientific interest for thrombolysis enhancement in combination with thrombolytic agents and microbubbles (MBs). The aim of the study was to develop an in vitro model to observe how the effects of sonothrombolysis change in the case where a tissue-mimicking material (TMM) is placed in the path of the US beam before the clot. Methods: Fully retracted blood clots were prepared and pulse sonicated for 1 h under various conditions. The system was in a state of real circulating flow with a branch of an open bypass and an occluded tube containing a blood clot, thus mimicking the case of ischemic stroke. The effectiveness of thrombolysis was quantified in milligrams of clots removed. An agar-based TMM was developed around the occluded tube. Results: The clot breakdown in a TMM was found to be more pronounced than in water, presumably due to the retention of the acoustic field. A higher level of acoustic power was required to initiate clot lysis (>76 W acoustic power) using only focused US (FUS). The greatest thrombolysis enhancement was observed with the largest chosen pulse duration (PD) and the use of MBs (150 mg clot mass lysis). The synergistic effect of FUS in combination with MBs on the enzymatic fibrinolysis enhanced thrombolysis efficacy by 260% compared to thrombolysis induced using only FUS. A reduction in the degree of clot lysis was detected due to the attenuation factor of the intervening material (30 mg at 1 and 4 ms PD). Conclusion: In vitro thrombolytic models including a TMM can provide a more realistic evaluation of new thrombolytic protocols. However, higher acoustic power should be considered to compensate for the attenuation factor. The rate of clot lysis is slow and the clinical use of this method will be challenging.

Resumen: Introducción y objetivo: : La isquemia arterial es una complicación infrecuente durante la canalización de una arteria; sin embargo, puede ocurrir durante su realización para la monitorización de un paciente neonatal. Este documento trata de reunir las principales recomendaciones acerca del mejor manejo de la isquemia arterial y así poder ser de utilidad en la práctica clínica médica. Casos clínicos: Se describen los casos de dos recién nacidos pretérmino que desarrollaron resultados adversos tras la canalización arterial, siendo preciso una intervención quirúrgica. En uno de ellos fue necesario la amputación del miembro inferior; en el otro, la realización de una fasciotomía. Conclusión: En este documento se resumen los datos más recientes publicados en relación con el tratamiento médico y quirúrgico de la isquemia arterial, así como del control del dolor asociado. El manejo de esta patología continúa siendo un reto debido a la escasa literatura existente de esta complicación en la población neonatal. Abstract: Introduction and objective: Arterial ischemia is an uncommon complication of arterial cannulation. Nonetheless, this condition may occur in neonatal population. This paper seeks to gather the main recommendations with regards to arterial ischemia management so as to be useful for physicians in their clinical practice. Case reports: The cases of two preterm newborns who developed adverse outcomes requiring surgical intervention derived from femoral arterial cannulation are presented. One patient required lower limb amputation; the other one, a fasciotomy. Conclusion: We summarize the most recent published data, concerning both medical and surgical ischemia treatment and associated pain control. Arterial ischemia management remains a challenge to physicians as there is limited data available about the best management of arterial ischemia in the neonatal population.

Blood clots are one of the leading causes of death as a consequence of cardiovascular disease in the first place. Design and synthesis of new thrombolytic drugs is aimed at the prevention of side effects one of the important target in medicine. Herein, we report a novel nano-composite prepared by Urokinase with magnetite nanoparticles (Fe3O4@MCM-41-Urokinase). The magnetic nano-drug was prepared in three steps: (i) preparation of colloidal iron oxide magnetite nanoparticles (Fe3O4 MNPs) with particle size lower than 8.0 nm, (ii) development of an organic–inorganic MCM-41 mesoporous structure on the surface of MNPs (Fe3O4@MCM-41) and (iii) load the Urokinase on synthesized nano-composite surface (Fe3O4@MCM-41-Urokinase). The prepared organic–inorganic magnetic nano-drug was characterized by FT-IR (Fourier transform infrared spectroscopy), XRF (X-ray fluorescence), XRD (X-ray powder diffraction), TEM (Transmission electron microscopy) and VSM (Vibrating-sample magnetometer). The TEM image show, a large number of magnetite nanoparticles (2–5 nm) are dispersed in the structure of the siliceous mesoporous. shows excellent activity in the drug delivery in rats. The synthesized nano drug showed good stability to environmental factors. The drug delivery was evaluated in a group of 16 rats, the results showed that drug delivery in the presence of a magnetic field was successfully carried out. [ABSTRACT FROM AUTHOR]

Thrombolytic agent therapy for acute ischemic stroke within 3 hours of the golden time can reduce mortality with disability and long-term care costs. This article describes the nursing experience of caring for an ischemic stroke patient who received thrombolytic agent therapy. From January 8 to January 10 in 2019, the assessment included interview, observation and physical assessment strategies. The confirmed major nursing problems were impaired physical mobility, risk for injury, anxiety and risk for infection. The first priority was to assist the patient and patient's family to understand stroke and the precautions of thrombolytic agent therapy with the aim of elevating relevant knowledge and ability of caring in the acute stage. Through drawing up the rehabilitation programs with patient and family to enhancing the patient's self-care ability, we aimed to relieve the patient's anxiety in a short time, and increase resilience which can be used to improve the patient's self-care and side limb training. The author hopes that this article can serve as a clinical care reference for other nurses taking care of similar cases in the future. [ABSTRACT FROM AUTHOR]

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A novel thrombolytic enzyme was produced by food grade microorganism Neurospora crassa using agro-industrial by-products as substrates. Process parameters were optimized using Plackett–Berman and Box–Benhken design. Under the optimized fermentation conditions, high fibrinolytic activity of 403.59 U/mL was obtained. It was purified with a specific activity of 3572.4 U/mg by ammonium sulfate precipitation and SP Sepharose chromatography. The molecular weight of the enzyme was approximately 32 kDa. It exhibited maximum activity at 40 °C and pH 7.4. Its activity was enhanced by Cu2+, Na+, Zn2+, and completely inhibited by phenylmethanesulfonyl fluoride, soybean trypsin inhibitor, aprotinin, which indicates it could be a serine protease. The enzyme could degrade fibrin clot directly without the need of plasminogen activator, and effectively cleaved Aα, Bβ, γ chains of fibrinogen. It could inhibit the formation of blood clots in vitro and acts as an anticoagulant. Compared to heparin the purified enzyme showed extended anticoagulant activity. Blood clots were dissolved effectively and dissolution rate was increased with time. Based on these results, this novel enzyme has the potential to be developed as a thrombolytic agent. [ABSTRACT FROM AUTHOR]

Abstract Fibrinolytic enzymes are considered promising alternative in the treatment of cardiovascular diseases by preventing fibrin clots. A protease from Mucor subtilissimus UCP 1262 was obtained by solid state fermentation and purified by ion exchange chromatography. The purified extract was administered at an acute dose of 2000 mg/mL to evaluate its toxic effects to the lungs of mice. After 14 days of treatment, a histomorphometric study was performed by the type 1 and 2 pneumocyte count and the evaluation of the lung area. As result, the experimental group showed a significant decrease of type 2 pneumocyte and although a decrease in the alveolar area was observed in relation to the control group, no significant pulmonary toxicity, emphysema, and fibrosis characteristics were detected. The in vitro tests suggest possible clinical applications for the enzyme.

Staphylokinase (Sak), a small 15 kDa globular protein that is secreted by certain strains of Staphylococcus aureus , shows a potent fibrin-selective thrombolytic activity. Earlier work has shown that Sak could potentially become a low-cost alternative to currently used thrombolytic agents, such as tissue plasminogen activator (tPA). In attempts to improve its potential for clinical applications, numerous modifications of Sak have already been investigated. Here, we have characterized a novel Sak modification, cyclized Sak (cyc-Sak), which was prepared through split-intein mediated protein backbone cyclization. We have characterized the structure, stability and the activity of cyc-Sak using biophysical techniques, limited proteolysis studies and plasminogen (PG)-activation assays. Our results show that cyc-Sak possesses an identical structure, enhanced stability, resistance to proteolysis by exoproteases and improved PG-activation properties compared to its linear counterpart. It can be over-expressed with high yield in the cytoplasm of Escherichia coli and is easily purified in a two-step process. The intein-mediated cyclization occurs spontaneously in vivo during protein expression and does not necessitate further modification steps after purification of the protein. Furthermore, covalent Sak cyclization could be readily combined with other Sak modifications previously proposed, to generate an effective thrombolytic agent with lower immunogenicity and improved stability and activity. [ABSTRACT FROM AUTHOR]

The demand for microbial thrombolytic agents is alarmingly increasing, and the discovery of novel microbial species with significant level of fibrinolytic enzyme production are required to cope up with the current circumstances. Surprisingly, marine fungi remain largely unexplored in this regard, presenting an untapped potential for the production of fibrinolytic enzymes. A novel marine fungal strain (Penicillium steckii KU1) was isolated successfully from Kappil beach, Kerala. At the beginning Czapek-dox media was used for the production of fibrinolytic enzyme. Statistical optimization of the enzyme production was achieved initially by Plackett-Burman design (PB). Interactive effect of various process parameters was further scrutinized by Central Composite Design (CCD). Incubation time, inoculum size and concentration of casein were shown significant contribution towards production. Statistical optimization, resulted in a tenfold increment (454.49 ± 14.66 U/mL) [optimized conditions - 30 °C, pH 7, casein 2.7 % (w/v), inoculum 5.75 million spores/mL and 115 h incubation], against the predicted value 441.42 U/mL. [Display omitted] • Fibrinolytic enzyme producing marine fungi was isolated and identified as Penicillium steckii KU 1. • Process parameters were optimized for enzyme production using Response surface methodology. • Optimum conditions were incubation time 115 h, inoculum size 5.75 million spores/mL and casein concentration 2.7 % w/v. • The mean activity (454.49 ± 14.66 U/mL), was found to be near to the predicted activity from the model (441.42 U/mL). • Final optimization of process parameters resulted in a tenfold increment in enzyme yield. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) like stroke and heart attack are leading causes of mortality worldwide, resulting in about 30% of deaths. The proportion in the Kingdom of Saudi Arabia was 46%. The commercial thrombolytic agents are thus associated with a range of side effects, while bacterially derived fibrinolytic enzymes have no or little side effects. Hence, there is an urgent need to identify novel fibrinolytic enzymes to treat or prevent CVDs. An endophytic bacterial strain producing fibrinolytic enzyme was isolated from the root of the plant Aloe castellorum. Enzyme production was enhanced through a conventional method and a statistical approach. The in vitro lytic activity of blood clots was also assessed. Endangered plant of Aloe castellorum roots, researchers isolated an endophytic strain producing fibrinolytic enzymes. It was identified as Brevibacterium sp. The culture medium was also optimized by a conventional method to screen the factors significant for successful culture. Fibrinolytic enzyme production peaked when Brevibacterium sp. was cultured in the presence of maltose (613 ± 12 U/mL), followed by starch (576 ± 13 U/mL). Among the selected nitrogen sources, yeast extract (642 ± 5.9 U/mL) and beef extract (610 ± 13 U/mL) enhanced enzyme yield relative to that in the control (487 ± 7.2 U/mL). Ionic sources such as Mg2+ (672 ± 10.3 U/mL) and Ca2+ (605 ± 12.3 U/mL) showed enhanced fibrinolytic enzyme production relative to the control (405 ± 13.2 U/mL). Upon employing a two-level full factorial design for examining the significant factors, it was revealed that maltose, yeast extract, and Mg2+ were important (p

One in five ischaemic strokes affects the posterior circulation. Basilar artery occlusion is a type of posterior circulation stroke associated with a high risk of disability and mortality. Despite its proven efficacy in ischaemic stroke more generally, alteplase only achieves rapid reperfusion in ~4% of basilar artery occlusion patients. Tenecteplase is a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, which can be administered by intravenous bolus. The single-bolus administration of tenecteplase vs. an hour-long alteplase infusion is a major practical advantage, particularly in “drip and ship” patients with basilar artery occlusion who are being transported between hospitals. Other practical advantages include its reduced cost compared to alteplase. The EXTEND-IA TNK trial demonstrated that tenecteplase led to higher reperfusion rates prior to endovascular therapy (22 vs. 10%, non-inferiority p = 0.002, superiority p = 0.03) and improved functional outcomes (ordinal analysis of the modified Rankin Scale, common odds ratio 1.7, 95% CI 1.0–2.8, p = 0.04) compared with alteplase in large-vessel occlusion ischaemic strokes. We recently demonstrated in observational data that tenecteplase was associated with increased reperfusion rates compared to alteplase prior to endovascular therapy in basilar artery occlusion [26% (n = 5/19) of patients thrombolysed with TNK vs. 7% (n = 6/91) thrombolysed with alteplase (RR 4.0 95% CI 1.3–12; p = 0.02)]. Although randomized controlled trials are needed to confirm these results, tenecteplase can be considered as an alternative to alteplase in patients with basilar artery occlusion, particularly in “drip and ship” patients.

One in five ischaemic strokes affects the posterior circulation. Basilar artery occlusion is a type of posterior circulation stroke associated with a high risk of disability and mortality. Despite its proven efficacy in ischaemic stroke more generally, alteplase only achieves rapid reperfusion in ~4% of basilar artery occlusion patients. Tenecteplase is a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, which can be administered by intravenous bolus. The single-bolus administration of tenecteplase vs. an hour-long alteplase infusion is a major practical advantage, particularly in "drip and ship" patients with basilar artery occlusion who are being transported between hospitals. Other practical advantages include its reduced cost compared to alteplase. The EXTEND-IA TNK trial demonstrated that tenecteplase led to higher reperfusion rates prior to endovascular therapy (22 vs. 10%, non-inferiority p = 0.002, superiority p = 0.03) and improved functional outcomes (ordinal analysis of the modified Rankin Scale, common odds ratio 1.7, 95% CI 1.0–2.8, p = 0.04) compared with alteplase in large-vessel occlusion ischaemic strokes. We recently demonstrated in observational data that tenecteplase was associated with increased reperfusion rates compared to alteplase prior to endovascular therapy in basilar artery occlusion [26% (n = 5/19) of patients thrombolysed with TNK vs. 7% (n = 6/91) thrombolysed with alteplase (RR 4.0 95% CI 1.3–12; p = 0.02)]. Although randomized controlled trials are needed to confirm these results, tenecteplase can be considered as an alternative to alteplase in patients with basilar artery occlusion, particularly in "drip and ship" patients. [ABSTRACT FROM AUTHOR]

Introduction: Measurement of thrombolytic activity is crucial for research and development of novel thrombolytics. It is a key factor in the assessment of the effectiveness of conventionally used thrombolytic therapies in the clinic. Previous methods used for the assessment of thrombolytic activity are often associated with some drawbacks such as being costly, time-consuming, complex with low accuracy. Here, we introduce a simple, economic, relatively accurate and fast method of spectrophotometric analysis of thrombolytic activity (SATA) assay, standardized by tissue plasminogen activator (tPA), which can quantitatively measure in vitro thrombolytic activity. Methods: Blood clots were formed, uniformly, by mixing citrated whole blood with partial thromboplastin time (PTT) reagent, together with calcium chloride. Then, designated concentrations of tPA were added to the samples, and the released red blood cells from each clot were quantified using spectrophotometry (λmax=405nm) as an indicator of thrombolytic activity. The accuracy of the method was tested by assessment of dose-responsibility against R2 value obtained by linear equation and measurement of the limit of detection (LOD) and limit of quantification (LOQ). The SATA assay was validated in comparison with some currently used techniques. Results: A linear relationship was obtained between different concentrations of tPA versus the spectrophotometric absorbance of the related dilutions of lysed clots, at λmax=405nm. Calculated R2 values were greater than 0.9; with LOD of 0.90 µg/mL of tPA (436.50IU) and LOQ of 2.99 µg/mL of tPA (1450.15IU). Conclusions: Conclusively, the SATA assay is a very simple quantitative method with repeatable and reproducible results for estimating the potency of an unknown thrombolytic agent, and calculating the activity as delicate as 1 µg/mL of tPA (485 IU/mL of thrombolytic dose).

Objective: To ascertain the efficacy, cost effectiveness and safety of streptokinase as intraluminal thrombolytic for occluded tunneled catheters in dialysis patients of a tertiary care hospital. Study Design: Prospective quasi-experimental study. Place and Duration of Study: Department of Nephrology, Pak Emirates Military Hospital Rawalpindi, from Aug 2018 to Jan 2019. Methodology: The sample population comprised of 66 patients with occluded tunneled HD catheters who received either streptokinase in a dose of 250,000 unit or 375,000 units. Primary endpoint was the proportion of patients with occluded catheters achieving post-thrombolytic blood flow of ≥300 mL/min which persists for about 30min of hemodialysis. Safety endpoints included the adverse complications like bleeding or any serious allergic reaction. Results: Out of 60 patients, 30 patients were treated with streptokinase in a dose of 375,000 units and 30 patients with 250,000 units of streptokinase. Hypertension and diabetes were the main causes of end-stage renal disease (50% vs 40%, p=0.08 and 33% vs 33%, p=0.38, respectively) jugular vein as main vascular access (54.8% vs 62.5%, p=0.57). Primary success was achieved in 60% in the first group and 42% in the second group, p=0.012. Patency was not achieved after the second dose in 10% in group-1 and 6.6% in the second group (p=0.31). Conclusion: Streptokinase, although its efficacy as intraluminal thrombolytic agents is shrouded in disputation but still can be used as a robust and economical thrombolytic agent for occluded HD catheters in our country. [ABSTRACT FROM AUTHOR]

Background: Immunogenicity of Streptokinase, as a thrombolytic drug, has limited its clinical use. Elimination of the amino acid residues that are responsible for immunogenicity while don’t affect the bioactivity of streptokinase is worthy. Recently, we modified the streptokinase through the elimination of 42 amino acids from its’ C-terminal and assessed its bioactivity in vitro. In this study, bioactivity of the mutated-streptokinase determined and compared with those of commercially available streptokinase (Heberkinase) in rabbits with induced blood clot.Materials and Methods: . Recombinant mutated streptokinase was purified and its lipopolysaccharide contained remove and evaluated by LAL test. Thrombolytic activity of drug was evaluated by rabbit jugular vein as in vivo thrombosis model. The thrombolytic property of the drug was evaluated with determining of D-dimer in plasma.Results:. The results showed in vivo bioactivity of both truncated and commercial streptokinase (pConclusion: Clinical use of the r-streptokinase requires more modification to restore its’ activity in vivo. This product may be a promising choice for clinical use after confirmation of its stability and non-immunogenicity.

Tetraselmis subcordiformis, a unicellular marine green alga, is used widely in aquaculture as an initial feeding for fish, bivalve mollusks, penaeid shrimp larvae, and rotifers because of its rich content of amino acids and fatty acids. A stable nuclear transformation system using the herbicide phosphinothricin (PPT) as a selective reagent was established previously. In this research, the recombinant expression in T. subcordiformis was investigated by particle bombardment with the rt-PA gene that encodes the recombinant human tissue-type plasminogen activator (Reteplase), which is a thrombolytic agent for acute myocardial infarction treatment. Transgenic algal strains were selected by their resistance to PPT, and expression of rt-PA was validated by PCR, Southern blotting, and Western blotting, and bioactivity of rt-PA was confirmed by the fibrin agarose plate assay for bioactivity. The results showed that rt-PA was integrated into the genome of T. subcordiformis, and the expression product was bioactive, indicating proper post-transcriptional modification of rt-PA in T. subcordiformis. This report contributes to efforts that take advantage of marine microalgae as cell factories to prepare recombinant drugs and in establishing a characteristic pathway of oral administration in aquaculture.

Acute pulmonary embolism (PE) carries a high risk of morbidity and mortality. Delays in diagnosis or therapy may result in sudden, fatal deterioration; therefore, rapid diagnosis and an appropriate therapeutic approach are needed. We aimed to investigate the effect of delaying thrombolytic administration on the mortality rate in a suspected PE. We retrospectively analyzed 49 consecutive patients who were aged 18 years or older and received thrombolysis for a high-risk PE without a major contraindication. All patients were classified according to the time of onset of the thrombolytic therapy. Patients experiencing cardiopulmonary arrest were analyzed from the time of admission to thrombolytic administration with 10-minute cutoff values. Data were analyzed by a regression analysis and a receiver operating characteristic (ROC) analysis for significant and independent associated risk factors and in-hospital mortality. Mortality was seen in 17 of the 49 cases. Thirteen of these had received thrombolytic therapy 1 hour after their emergency department (ED) admission. Among all cases, the mortality rate was 35%. The ROC analysis indicated that a > 97-second delayed thrombolytic administration time was associated with mortality with 53% sensitivity and 91% specificity (area under the curve, 0.803; 95% confidence interval, 0.668–0.938). In the logistic regression, a 5-minute delay in thrombolytic therapy (beta = 1.342; 95% confidence interval, 1.818–2.231; p = 0.001) was associated with in-hospital mortality in the multivariable model. No major bleeding complications were seen in PE survivors. We conclude that early onset thrombolytic therapy in the ED for high-risk and hemodynamically worsening patients appears safe and life-saving.

Background: Agro-wastes were used for the production of fibrinolytic enzyme in solid-state fermentation. The process parameters were optimized to enhance the production of fibrinolytic enzyme from Bacillus halodurans IND18 by statistical approach. The fibrinolytic enzyme was purified, and the properties were studied. Results: A two-level full factorial design was used to screen the significant factors. The factors such as moisture, pH, and peptone were significantly affected enzyme production and these three factors were selected for further optimization using central composite design. The optimum medium for fibrinolytic enzyme production was wheat bran medium containing 1% peptone and 80% moisture with pH 8.32. Under these optimized conditions, the production of fibrinolytic enzyme was found to be 6851 U/g. The fibrinolytic enzyme was purified by 3.6-fold with 1275 U/mg specific activity. The molecular mass of fibrinolytic enzyme was determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis, and it was observed as 29 kDa. The fibrinolytic enzyme depicted an optimal pH of 9.0 and was stable at a range of pH from 8.0 to 10.0. The optimal temperature was 60°C and was stable up to 50°C. This enzyme activated plasminogen and also degraded the fibrin net of blood clot, which suggested its potential as an effective thrombolytic agent. Conclusions: Wheat bran was found to be an effective substrate for the production of fibrinolytic enzyme. The purified fibrinolytic enzyme degraded fibrin clot. The fibrinolytic enzyme could be useful to make as an effective thrombolytic agent.

Agro-residues were used as the substrate for the production of fibrinolytic enzyme in solid state fermentation. In this study, two-level full factorial design (25) and response surface methodology were applied to optimize a fermentation medium for the production of fibrinolytic enzyme from the marine isolate Shewanella sp. IND20. The 25 factorial design demonstrated that the physical factors (pH and moisture) and nutrient factors (trehalose, casein, and sodium dihydrogen phosphate) had significant effect on fibrinolytic enzyme production. Central composite design was employed to search for the optimal concentration of the three factors, namely moisture, pH, and trehalose, and the experimental results were fitted with a second-order polynomial model at 99% level (p

Introduction: Measurement of thrombolytic activity i.e. clot lysis is crucial for research and development of novel thrombolytics. It is also a key factor in assessment of the effectiveness of conventionally used thrombolytic agents in the clinic, which are the choice effective therapies for myocardial infarction and ischemic stroke. Previous methods used for the assessment of thrombolytic activity are often associated with some drawbacks such as being costly, time-consuming, complication and low accuracy. Here, we introduce a simple, economic, relatively accurate and fast method of spectrophotometric analysis of thrombolytic activity (SATA) assay, standardized by tissue plasminogen activator (tPA), which can quantitatively measure in vitro thrombolytic activity. Methods: Blood clots were formed, uniformly, by mixing citrated whole blood with partial thromboplastin time (PTT) reagent, together with calcium chloride. Then, designated concentrations of tPA were added to the samples, and the released red blood cells from each clot were quantified using spectrophotometry (λmax= 405 nm) as an indicator of thrombolytic activity. The accuracy of the method was tested by assessment of dose-responsibility against R2 value obtained by linear equation and measurement of limit of detection (LOD) and limit of quantification (LOQ). The SATA assay was validated in comparison with some currently used techniques. Results: A linear relationship was obtained between different concentrations of tPA versus the spectrophotometric absorbance of the related dilutions of lysed clots, at λmax = 405 nm. Calculated R² values were greater than 0.9; with LOD of 0.90 µg/mL of tPA (436.50IU) and LOQ of 2.99 µg/mL of tPA (1450.15IU). Conclusion: Conclusively, the SATA assay is a very simple quantitative method with repeatable and reproducible results for estimating the potency of an unknown thrombolytic agent, and calculating the activity as delicate as 1 µg/mL of tPA (485 IU/mL of thrombolytic dose). [ABSTRACT FROM AUTHOR]