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https://www.readbyqxmd.com/read/28336948/plasminogen-activator-inhibitor-1-protects-mice-against-cardiac-fibrosis-by-inhibiting-urokinase-type-plasminogen-activator-mediated-plasminogen-activation
#1
Kamlesh K Gupta, Deborah L Donahue, Mayra J Sandoval-Cooper, Francis J Castellino, Victoria A Ploplis
Plasminogen activator inhibitor-1 (PAI-1) is known to protect mice against cardiac fibrosis. It has been speculated that PAI-1 may regulate cardiac fibrosis by inactivating urokinase-type plasminogen activator (uPA) and ultimately plasmin (Pm) generation. However, the in vivo role of PAI-1 in inactivating uPA and limiting the generation of Pm during cardiac fibrosis remains to be established. The objective of this study was to determine if the cardioprotective effect of PAI-1 is mediated through its ability to directly regulate urokinase -mediated activation of plasminogen (Pg)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330184/potential-fibrinolytic-activity-of-an-endophytic-lasiodiplodia-pseudotheobromae-species
#2
Vineet Meshram, Sanjai Saxena
Cost-effective, fibrinolytic agents possessing least or no antigenic properties are much in demand for their prospective use as clot busters in thrombolytic therapy. The present communication explores the potential of 22 endophytic Botryosphaeria species isolated from stem of Aegle marmelos for their fibrinolytic potential. Only nine fungal isolates exhibited proteolytic activity out of which only four possessed plasminogen-independent fibrinolytic activity. The endophytic fungal isolate #1088 AMSTITYEL showed maximum in vitro proteolytic and fibrinolytic activity with a halo formation of 153...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28325863/pharmacological-targeting-of-plasmin-prevents-lethality-in-a-murine-model-of-macrophage-activation-syndrome
#3
Hiroshi Shimazu, Shinya Munakata, Yoshihiko Tashiro, Yousef Salama, Douaa Dhahri, Salita Eiamboonsert, Yasunori Ota, Haruo Onoda, Yuko Tsuda, Yoshio Okada, Hiromitsu Nakauchi, Beate Heissig, Koichi Hattori
Macrophage activation syndrome (MAS) is a life-threatening disorder characterized by a cytokine storm and multiorgan dysfunction due to excessive immune activation. Although abnormalities of coagulation and fibrinolysis are major components of MAS, the role of the fibrinolytic system and its key player, plasmin, in the development of MAS remains to be solved. We established a murine model of fulminant MAS by repeated injections of Toll-like receptor-9 (TLR-9) agonist and D-galactosamine (DG) in immunocompetent mice...
March 21, 2017: Blood
https://www.readbyqxmd.com/read/28323357/characterisation-of-clotting-factors-anticoagulant-protein-activities-and-viscoelastic-analysis-in-healthy-donkeys
#4
A Perez-Ecija, F J Mendoza
BACKGROUND: Studies have demonstrated differences in commonly measured hemostatic parameters between donkeys and horses. Whether clotting factors, anticoagulant protein activities and thromboelastography parameters also differ between species is still unknown. OBJECTIVES: To characterize hemostatic parameters in healthy donkeys and compare them to those of horses. STUDY DESIGN: Cross-sectional study. METHODS: Clotting Factors (V, VII, VIII, IX, X, XI and XII), and antithrombin III, Protein C and Protein S activities were measured in 80 healthy Andalusian and crossbred donkeys and 40 healthy Andalusian crossbred horses with assays based on human deficient plasmas...
March 21, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28320709/plasmin-and-plasminogen-induce-macrophage-reprogramming-and-regulate-key-steps-of-inflammation-resolution-via-annexin-a1
#5
Michelle A Sugimoto, Ana Luíza C Ribeiro, Bruno R C Costa, Juliana P Vago, Kátia M Lima, Fernanda S Carneiro, Mylena Maira O Ortiz, Graziele Letícia N Lima, Aline A F Carmo, Renata M Rocha, Denise A Perez, Alessandra C Reis, Vanessa Pinho, Lindsey A Miles, Cristiana C Garcia, Mauro M Teixeira, Lirlândia P Sousa
Inflammation resolution is an active process that functions to restore tissue homeostasis. Participation of the plasminogen/plasmin (Plg/Pla) system in the productive phase of inflammation is well known, but its involvement in the resolution phase remains unclear. Therefore, we aimed to investigate the potential role of Plg/Pla in key events during the resolution of acute inflammation and its underlying mechanisms. Plg/Pla injection into the pleural cavity of BALB/c mice induced a time-dependent influx of mononuclear cells that were primarily macrophages of anti-inflammatory (M2 - F4/80(high) Gr1(-) CD11b(high)) and proresolving (Mres - F4/80(med) CD11b(low)) phenotypes, without changing the number of macrophages with a pro-inflammatory profile (M1 - F4/80(low) Gr1(+) CD11b(med))...
March 20, 2017: Blood
https://www.readbyqxmd.com/read/28317410/sex-hormone-binding-globulin-and-antithrombin-iii-activity-in-women-with-oral-ultra-low-dose-estradiol
#6
Sumika Matsui, Toshiyuki Yasui, Kana Kasai, Kaoru Keyama, Kanako Yoshida, Takeshi Kato, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki, Minoru Irahara
Oral oestrogen increases the risk of venous thromboembolism (VTE) and increases production of sex hormone-binding globulin (SHBG) in a dose-dependent manner. SHBG has been suggested to be involved in venous thromboembolism. We examined the effects of oral ultra-low-dose oestradiol on circulating levels of SHBG and coagulation parameters, and we compared the effects to those of transdermal oestradiol. Twenty women received oral oestradiol (500 μg) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 μg) as a transdermal group...
March 20, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28304250/tranexamic-acid-and-supportive-measures-to-treat-wasting-marmoset-syndrome
#7
Takuro Yoshimoto, Kimie Niimi, Eiki Takahashi
Wasting marmoset syndrome (WMS) has high incidence and mortality rates and is one of the most important problems in captive common marmoset (Callithrix jacchus) colonies. Despite several reports on WMS, little information is available regarding its reliable treatment. We previously reported that marmosets with WMS had high serum levels of matrix metalloproteinase 9 (MMP9). MMP9 is thought to be a key enzyme in the pathogenesis of inflammatory bowel disease, the main disease state of WMS, and is activated by plasmin, a fibrinolytic factor...
December 1, 2016: Comparative Medicine
https://www.readbyqxmd.com/read/28303518/potentially-life-threatening-coagulopathy-associated-with-simultaneous-reduction-in-coagulation-and-fibrinolytic-function-in-pediatric-acute-leukemia-after-hematopoietic-stem-cell-transplantation
#8
Takashi Ishihara, Keiji Nogami, Tomoko Matsumoto, Akitaka Nomura, Yasufumi Takeshita, Satoshi Ochi, Midori Shima
The pathogenesis of sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) is poorly understood, and limited information is available on global hemostatic function in HSCT. We assessed changes in coagulation and fibrinolysis using a simultaneous thrombin and plasmin generation assay (T/P-GA) during HSCT. Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) using T/P-GA in six pediatric acute leukemia patients treated with HSCT were compared to normal plasma...
March 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28302935/factor-x-deficiency-with-heterozygous-mutations-of-novel-p-g435s-and-known-p-g244r-in-a-patient-presenting-with-severe-umbilical-hemorrhage
#9
Yoko Matsuo, Tatsuki Mizuochi, Miho Mitsuo, Shinichiro Nakagawa, Shuichi Ozono, Koichiro Ueda, Yoko Sogabe, Ritsuko Seki, Kenji Soejima, Takashi Okamura, Yushiro Yamashita
A 10-day-old male patient was referred to our hospital with severe umbilical bleeding. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prominently prolonged. Plasma coagulation factor X (FX) activity and antigen levels were 1% and 0.6%, respectively. A DNA sequence analysis of his leukocytes revealed a compound heterozygous state; known Gly244 to Arg (p.G244R) in exon 6 and a novel mutation of Gly 435 to Ser (p.G435S) in exon 8. A pedigree analysis showed that p.G244R originated from the paternal side, while p...
March 15, 2017: Kurume Medical Journal
https://www.readbyqxmd.com/read/28283893/tranexamic-acid-in-the-treatment-of-melasma-a-review-of-the-literature
#10
REVIEW
Marina Perper, Ariel Eva Eber, Rachel Fayne, Sebastian Hugo Verne, Robert James Magno, Jessica Cervantes, Mana ALharbi, Ibrahim ALOmair, Abdulkarem Alfuraih, Keyvan Nouri
Melasma is a common acquired pigmentary disorder marked by irregular hyperpigmented macules or patches and most commonly occurs in women of darker skin color. It is a chronic often-relapsing condition that causes negative psychosocial effects in those affected. Current treatments such as hydroquinone, kojic acid, and retinoids, among others, demonstrate variable efficacy and side-effect profiles. We conducted a comprehensive literature review examining the use of tranexamic acid (TA), a well-known anti-fibrinolytic agent, in the treatment of melasma...
March 10, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28279966/plasmin-cleaves-von-willebrand-factor-at-k1491-r1492-in-the-a1-a2-linker-region-in-a-shear-and-glycan-dependent-manner-in-vitro
#11
Teresa M Brophy, Soracha E Ward, Thomas R McGimsey, Sonja Schneppenheim, Clive Drakeford, Jamie M O'Sullivan, Alain Chion, Ulrich Budde, James S O'Donnell
OBJECTIVE: Previous studies have demonstrated a role for plasmin in regulating plasma von Willebrand factor (VWF) multimer composition. Moreover, emerging data have shown that plasmin-induced cleavage of VWF is of particular importance in specific pathological states. Interestingly, plasmin has been successfully used as an alternative to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif) in a mouse model of thrombotic thrombocytopenic purpura. Consequently, elucidating the molecular mechanisms through which plasmin binds and cleaves VWF is not only of basic scientific interest but also of direct clinical importance...
March 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28275164/plasminogen-deficiency-delays-the-onset-and-protects-from-demyelination-and-paralysis-in-autoimmune-neuroinflammatory-disease
#12
Maureen A Shaw, Zhen Gao, Kathryn E McElhinney, Sherry Thornton, Matthew J Flick, Adam Lane, Jay L Degen, Jae Kyu Ryu, Katerina Akassoglou, Eric S Mullins
Multiple Sclerosis (MS) is a neuroinflammatory, demyelinating disease of the central nervous system. Fibrin(ogen) deposition at sites of blood brain barrier breakdown is a prominent feature of neuroinflammatory disease and contributes to disease severity. Plasminogen, the primary fibrinolytic enzyme, also modifies inflammatory processes. We used a murine model of MS, experimental autoimmune encephalomyelitis (EAE), to evaluate the hypothesis that the loss of plasminogen would exacerbate neuroinflammatory disease...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28273315/extracellular-collagen-promotes-interleukin-1%C3%AE-induced-urokinase-type-plasminogen-activator-production-by-human-corneal-fibroblasts
#13
Koji Sugioka, Aya Kodama-Takahashi, Koji Yoshida, Keiichi Aomatsu, Kiyotaka Okada, Teruo Nishida, Yoshikazu Shimomura
Purpose: Keratocytes maintain homeostasis of the corneal stroma through synthesis, secretion, and degradation of collagen fibrils of the extracellular matrix. Given that these cells are essentially embedded in a collagen matrix, keratocyte-collagen interactions may play a key role in regulation of the expression or activation of enzymes responsible for matrix degradation including urokinase-type plasminogen activator (uPA), plasmin, and matrix metalloproteinases (MMPs). We examined the effect of extracellular collagen on the production of uPA by corneal fibroblasts (activated keratocytes) stimulated with the proinflammatory cytokine interleukin-1β (IL-1β)...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28270519/plasminogen-activator-inhibitor-1-regulates-macrophage-dependent-postoperative-adhesion-by-enhancing-egf-her1-signaling-in-mice
#14
Kumpei Honjo, Shinya Munakata, Yoshihiko Tashiro, Yousef Salama, Hiroshi Shimazu, Salita Eiamboonsert, Douaa Dhahri, Atsuhiko Ichimura, Takashi Dan, Toshio Miyata, Kazuyoshi Takeda, Kazuhiro Sakamoto, Koichi Hattori, Beate Heissig
Adhesive small bowel obstruction remains a common problem for surgeons. After surgery, platelet aggregation contributes to coagulation cascade and fibrin clot formation. With clotting, fibrin degradation is simultaneously enhanced, driven by tissue plasminogen activator-mediated cleavage of plasminogen to form plasmin. The aim of this study was to investigate the cellular events and proteolytic responses that surround plasminogen activator inhibitor (PAI-1; Serpine1) inhibition of postoperative adhesion. Peritoneal adhesion was induced by gauze deposition in the abdominal cavity in C57BL/6 mice and those that were deficient in fibrinolytic factors, such as Plat(-/-) and Serpine1(-/-) In addition, C57BL/6 mice were treated with the novel PAI-1 inhibitor, TM5275...
March 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28266313/development-of-a-plasminogen-activator-inhibitor-pai-1-assay-and-comparison-of-plasma-pai-1-activity-in-hyperlipidemic-dyslipidemic-dogs-with-either-hyperadrenocorticism-or-diabetes-mellitus-and-healthy-dogs
#15
Cheryl J Wong, Michael Koch, Erica L Behling-Kelly
Thrombosis is a serious complication of many canine diseases and may be related to decreased fibrinolytic potential. Plasminogen activator inhibitor-1 (PAI-1) is the key regulator of fibrinolysis with increased levels demonstrated in states of pro-thrombosis and abnormal lipid metabolism. Our objective was to develop and validate a canine PAI-1 activity assay and test whether dogs with hyperadrenocorticism or diabetes mellitus that are hyperlipidemic/dyslipidemic have increased plasma PAI-1 activity. Functionally active PAI-1 in the plasma sample was incubated with recombinant tissue plasminogen activator (tPA), allowing the formation of a 1:1 stoichiometric inactive complex...
November 8, 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/28262301/effects-of-alcohol-on-postoperative-adhesion-formation-in-ischemic-myocardium-and-pericardium
#16
Nassrene Y Elmadhun, Ashraf A Sabe, Antonio D Lassaletta, Rahul S Dalal, Frank W Sellke
BACKGROUND: Postoperative formation of adhesions increases risk of complications during cardiac reoperations. We previously demonstrated that swine supplemented with vodka had a significant reduction in adhesions at sternotomy after previous thoracotomy. This follow-up study was conducted to determine reproducibility and the mechanism for adhesion reduction in swine supplemented with ethanol. METHODS: An ameroid constrictor was placed in the left circumflex in 14 male Yorkshire swine to induce chronic myocardial ischemia through left minithoracotomy...
March 2, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28236848/the-fibrinolytic-system-a-new-target-for-treatment-of-depression-with-psychedelics
#17
R D Idell, G Florova, A A Komissarov, S Shetty, R B S Girard, S Idell
Current understanding of the neurobiology of depression has grown over the past few years beyond the traditional monoamine theory of depression to include chronic stress, inflammation and disrupted synaptic plasticity. Tissue plasminogen activator (tPA) is a key factor that not only promotes fibrinolysis via the activation of plasminogen, but also contributes to regulation of synaptic plasticity and neurogenesis through plasmin-mediated activation of a probrain derived neurotrophic factor (BDNF) to mature BDNF...
March 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28236528/the-nature-and-consequence-of-vitronectin-interaction-in-the-non-compromised-contact-lens-wearing-eye
#18
Manpreet Cooner, Aisling Mann, Brian Tighe
PURPOSE: The aim of this work was to investigate the locus and extent of vitronectin (Vn) deposition on ex vivo contact lenses and to determine the influence of wear modality together with surface and bulk characteristics of the lens material. METHODS: The quantity and location of Vn deposition on the surfaces of contact lens materials was investigated using a novel on-lens cell attachment assay technique. RESULTS: Vn mapping showed that deposition resulted from lens-corneal interaction rather than solely from the tear film...
February 21, 2017: Contact Lens & Anterior Eye: the Journal of the British Contact Lens Association
https://www.readbyqxmd.com/read/28219684/development-of-magnetic-nanoparticle-based-calorimetric-assay-for-the-detection-of-bovine-mastitis-in-cow-milk
#19
Raja Chinnappan, Sana Al Attas, Wendy E Kaman, Floris J Bikker, Mohammed Zourob
Mastitis in dairy cattle is an inflammatory reaction of the udder tissue. Mastitis increases plasmin levels, leading to an increased proteolysis of milk proteins such as casein, resulting in a significant decrease in milk quality and related dairy products. Due to its key-role in mastitis, we used plasmin proteolytic activity as a biomarker for the detection of mastitis in bovine mastitic milk. Inspired by earlier studies on protease activity using mastitic milk samples, we developed a simple colorimetric assay to distinguish mastitic milk from milk derived from healthy animals...
February 17, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28219085/fibrinolysis-in-trauma-myth-reality-or-something-in-between
#20
Mark Walsh, Jacob Shreve, Scott Thomas, Ernest Moore, Hunter Moore, Daniel Hake, Tim Pohlman, Patrick Davis, Victoria Ploplis, Andres Piscoya, Julie Wegner, John Bryant, Anton Crepinsek, James Lantry, Forest Sheppard, Francis Castellino
The emphasis on fibrinolysis as an important contributor to trauma-induced coagulopathy (TIC) has led to a debate regarding the relative clinical significance of fibrinolysis in the setting of trauma. The debate has centered on two camps. The one camp defines fibrinolysis in trauma by standard coagulation tests as well as fibrin split products, D-dimers, and plasmin/antiplasmin levels. This camp favors a more liberal use of tranexamic acid and attributes more significance to hyperfibrinolysis in TIC. The other camp favors a definition of fibrinolysis based on the viscoelastic tests (VET), rotational thromboelastometry (ROTEM), and thromboelastography (TEG)...
March 2017: Seminars in Thrombosis and Hemostasis
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