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The Potential of Plants as Treatments for Venous Thromboembolism
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Lilitha L. Denga, Namrita Lall
The aim of the fibrinolytic system is to resolve existing thrombi by cleaving fibrin to soluble degradation products. Plasmin is the enzyme that degrades fibrin, while plasminogen is the inactive precursor of plasmin (Anwar et al. 2011). Plasmin is created when plasminogen is released into the bloodstream and activated by tissue plasminogen activator (TPA) or urokinase plasminogen activator (UPA). TPA binds to clot-bound plasminogen and converts it to plasmin. UPA binds to the UPA receptors located on cell surfaces and converts cell-bound plasminogen to plasmin (Ezihe-ejiofor and Hutchinson 2013).
Metabolic Syndrome
Published in Jahangir Moini, Matthew Adams, Anthony LoGalbo, Complications of Diabetes Mellitus, 2022
Jahangir Moini, Matthew Adams, Anthony LoGalbo
The peritoneal adipocytes also excessively produce plasminogen activator inhibitor (PAI1), which directly opposes tissue plasminogen activator (TPA), decreasing formation of plasmin from plasminogen. In the systemic circulation, less plasmin means that fibrin breaks down slower, decreasing clot lysis and increasing thromboembolic events as well as making them more severe. Plasmin is also needed in vessel walls to degrade and remove collagen from atheromatous plaques, so that vascular smooth muscle cells can enter and replace collagen tissues. This entry stabilizes plaques, making rupture and cardiovascular events less likely. Elevated PAI1 in vessel walls occurs in metabolic syndrome and type 2 diabetes. However, TZDs can reduce PAI1 levels in metabolic syndrome patients. This partly explains reduced cardiovascular events seen when the TZD called pioglitazone is used.
Stroke and Transient Ischemic Attacks of the Brain and Eye
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
ALT is a single-chain recombinant form of tissue plasminogen activator (tPA), which cleaves plasminogen to plasmin. Plasmin is a serine protease that degrades fibrin (fibrinolysis) within the thrombus and dissolves it. Outside the thrombus, plasmin is rapidly inactivated by macroglobulin and antiplasmin. The half-life of ALT is short (4–5 minutes); hence, it is administered as an initial bolus followed by an infusion over 1 hour.
Testing strategies used in the diagnosis of rare inherited bleeding disorders
Published in Expert Review of Hematology, 2023
The key pro-enzyme plasminogen is proteolytically activated by plasminogen activators (tissue type (tPA) and urokinase (uPA)) to plasmin, which in turn degrades fibrin to soluble fibrin degradation products. tPA is produced by the vascular endothelium and binds to fibrin, and uPA is extravascular and primarily responsible for cell migration and tissue remodeling. Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor (SERPIN), inhibits the generation of plasmin; plasmin action is inhibited by α2-antiplasmin (α2-plasmin inhibitor), and α2-macroglobulin. Original assays evaluating fibrinolysis consisted of global assays of clot lysis performed on whole blood, plasma, or the euglobulin fraction of plasma [80]. Many of these assays lack standardization and are affected by fibrinogen and FXIII levels; hence, interlaboratory comparison is likely not possible. However, commercial assays for specific components of the fibrinolytic system are available [81]. Currently, the assessment of the fibrinolytic system consists of measurements of PAI-1 activity and antigen and α2-plasmin inhibitor activity.
Novel formulations for topical delivery of tranexamic acid: assessing the need of epidermal targeting for hyperpigmentation disorders
Published in Expert Opinion on Drug Delivery, 2023
Piyush Verma, Khushwant S. Yadav
Series of events are initiated in skin due to many internal and external triggers leading to hyperpigmentation. Figure 2 briefly gives the flow of events taking place in skin. Factors like ultraviolet (UV) light, oxidative stress, pregnancy, and oral contraceptives are the initiators for the hyperpigmentation process [26–30]. UV light and oxidative stress (induced by UV light and other factors such as smoking) upregulate keratinocytes, leading to the production of single-chain urokinase and plasminogen activator. Plasminogen activator causes activation plasmin peptide which leads to the activation of melanocytes by two means: single-chain urokinase and arachidonic acid pathway involving prostaglandins and interleukins [31]. Plasmin also activates vascular endothelial growth factor which leads to angiogenesis [32]. A series of events take place inside melanocytes as well which are depicted in Figure 2(b). When melanocyte is activated, phenylalanine gets converted into tyrosine which further gets converted into tyrosine, DOPA, dopaquinone in succession. Dopaquinone further produces two types of melanin, eumelanin and pheomelanin, which cause hyperpigmentation [33]. In the process, tyrosinase enzyme is involved in the conversion of tyrosine to DOPA and of DOPA to dopaquinone.
Factors affecting the dynamics and heterogeneity of the EPR effect: pathophysiological and pathoanatomic features, drug formulations and physicochemical factors
Published in Expert Opinion on Drug Delivery, 2022
Rayhanul Islam, Hiroshi Maeda, Jun Fang
Plasminogen activators secreted by tumor cells are important in cancer metastasis, but they can serve as EPR effect enhancers, a strategy that Zhang et al. [61] reported. Plasminogen is responsible in fibrinolysis to break down fibrin gel or fibrin clots after activation to plasmin in tumor blood vessels, or in the vicinity of tumor or stromal tissues, thereby restoring and improving tumor blood flow and opening endothelial gaps. Thus, barriers are removed and drug penetration and accumulation in tumors are facilitated. Mei et al. [62] also developed a novel approach with plasminogen activator incorporated into a redox-responsive nanoparticle; they found marked drug accumulation in tumors by virtue of the EPR effect and at the same time observed tumor suppression via reactive oxygen species and cytokine modulation.