Tissue plasminogen activator (tPA) is the only FDA approved medical treatment for the ischaemic stroke. However, it associates with some inevitable limitations, including: short therapeutic window, extremely short half-life and low penetration in large clots. Systemic administration may lead to complications such as haemorrhagic conversion in the brain and relapse in the form of re-occlusion. Furthermore, ultrasound has been utilised in combination with contrast agents, echogenic liposome, microspheres or nanoparticles (NPs) carrying tPA for improving thrombolysis - an approach that has resulted in slight improvement of tPA delivery and facilitated thrombolysis. Most of these delivery systems are able to extend the circulating half-life and clot penetration of tPA. Various technologies employed for ameliorated thrombolytic therapy are in different phases, some are in final steps for clinical applications while some others are under investigations for their safety and efficacy in human cases. Here, recent progresses on the thrombolytic therapy using novel nano- and micro-systems incorporating tPA are articulated. Of these, liposomes and microspheres, polymeric NPs and magnetic nanoparticles (MNPs) are discussed. Key technologies implemented for efficient delivery of tPA and advanced thrombolytic therapy and their advantages/disadvantages are further expressed.
Introduction: Humans manifest a behavioral inclination towards more utility of one side of the body, in relation with the dominant hemisphere of the brain. The current investigation assessed handedness together with chewing preference which have not been evaluated in various food textures before. Methods: Nineteen young and healthy volunteers chewed hard (walnut) and soft (cake) foods, during surface electromyography recording from masseter muscles. The side of the first and all chews in the two food types were determined and compared with the side of the dominant hand. Results: Results indicated the two lateralities in the same side considerably (60%-70%), implying the solidarity in the control of the dominant hemisphere of the brain. The unilaterality was more prominent in the assessment of all chews in hard food, with higher statistical agreement and correlation. Conclusion: Thereupon masticatory preference is found with probable origins in the dominant hemisphere of the brain.
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). 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).
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