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https://www.readbyqxmd.com/read/29882241/enzymatic-and-chemical-synthesis-of-new-anticoagulant-peptides
#1
Anabella Origone, Grisel Bersi, Andrés Illanes, Héctor Sturniolo, Constanza Liggieri, Fanny Guzmán, Sonia Barberis
In this study we report the enzymatic synthesis of N-α-[Carbobenzyloxy]-Tyr-Gln-Gln (Z-YQQ), a new anticoagulant tripeptide. It was obtained using phytoproteases from the stems and petioles of Asclepias curassavica L. as catalyst in an aqueous-organic biphasic system formed by 50% (v/v) ethyl acetate and 0.1 M Tris - HCl buffer pH 8. The resulting peptide was compared with the analogous peptide Tyr-Gln-Gln (YQQ) produced by solid-phase chemical synthesis. The in vitro anticoagulant activity of the above mentioned peptides was determined using Wiener Lab Test (Wiener, Argentina)...
June 8, 2018: Biotechnology Progress
https://www.readbyqxmd.com/read/29847383/mixing-studies-in-patients-with-prolonged-activated-partial-thromboplastin-time-or-prothrombin-time
#2
Honorio T Benzon, Meghan Park, Robert J McCarthy, Mark C Kendall, Paul F Lindholm
BACKGROUND: Patients presenting for surgery may have isolated or combined prolonged activated partial thromboplastin time (aPTT) and/or prothrombin time (PT). In patients not receiving anticoagulants or with no identifiable cause for abnormal clot formation, a mixing study is performed. The index of circulating anticoagulant (ICA) has been used to predict the presence of an inhibitor, usually a lupus anticoagulant. METHODS: We retrospectively reviewed the results of mixing studies performed at Northwestern Memorial Hospital, between January 1, 2010 and February 29, 2012...
May 25, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29758118/hemostasis-biomarkers-in-multiple-sclerosis
#3
Nicole Ziliotto, Francesco Bernardi, Dejan Jakimovski, Marcello Baroni, Giovanna Marchetti, Niels Bergsland, Deepa P Ramasamy, Bianca Weinstock-Guttman, Ferdinand Schweser, Paolo Zamboni, Murali Ramanathan, Robert Zivadinov
OBJECTIVE: To investigate the plasma levels of hemostasis components in multiple sclerosis (MS) and their association with clinical and MRI outcomes. METHODS: We studied 138 MS patients (85 with relapsing-remitting, RR-MS and 53 with progressive, P-MS) with mean age of 54 years; 72.5% female; median EDSS 3.5; mean disease duration 21 years) and 42 age- and sex-matched healthy individuals (HI). All subjects were examined with 3T MRI and clinical examinations. Plasma levels of hemostasis factors (procoagulant, factor XII, FXII) and inhibitors (tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), heparin cofactor II (HCII), disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13), and plasminogen activator inhibitor 1 (PAI-1) were evaluated by magnetic Luminex assays and ELISA...
May 14, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29747114/effect-of-double-filtration-plasmapheresis-for-antibody-mediated-rejection-on-hemostasis-parameters-and-thrombin-generation
#4
R Marlu, P Malvezzi, L Seyve, T Jouve, J Maurizi, F Defendi, P L Carron, M Christophe, A Le Gouellec, B Polack, L Rostaing
INTRODUCTION: Donor-specific alloantibodies (DSAs) cause kidney-allograft loss in chronic antibody-mediated rejection (CAMR). Treatment relies on blocking antibody-producing cells and removing DSAs by apheresis: e.g., double-filtration plasmapheresis (DFPP). MATERIALS AND METHODS: To determine the impact of DFPP (6 or 8 sessions/patient) on clotting factors and natural anticoagulants, and on thrombin generation, we performed a prospective and observational study in five CAMR kidney-transplant patients who received DFPP plus rituximab therapy...
April 20, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29731736/coagulation-factor-xii-levels-and-intrinsic-thrombin-generation-in-multiple-sclerosis
#5
Nicole Ziliotto, Marcello Baroni, Sofia Straudi, Fabio Manfredini, Rosella Mari, Erica Menegatti, Rebecca Voltan, Paola Secchiero, Paolo Zamboni, Nino Basaglia, Giovanna Marchetti, Francesco Bernardi
Background: Factor XII (FXII) activation initiates the intrinsic (contact) coagulation pathway. It has been recently suggested that FXII could act as an autoimmunity mediator in multiple sclerosis (MS). FXII depositions nearby dentritic cells were detected in the central nervous system of MS patients and increased FXII activity has been reported in plasma of relapsing remitting and secondary progressive MS patients. FXII inhibition has been proposed to treat MS. Objective: To investigate in MS patients multiple FXII-related variables, including the circulating amount of protein, its pro-coagulant function, and their variation over time...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29709596/vascular-aspects-of-the-ehlers-danlos-syndromes
#6
REVIEW
Fransiska Malfait
The Ehlers-Danlos Syndromes comprise a heterogeneous group of rare monogenic conditions that are characterized by joint hypermobility, skin and vascular fragility and generalized connective tissue friability. The latest classification recognizes 13 clinical subtypes, with mutations identified in 19 different genes. Besides defects in fibrillar collagens (collagen types I, III and V), their modifying enzymes (ADAMTS-2, lysylhydroxylase 1 (LH1)), and molecules involved in collagen folding (FKBP22), defects have recently been identified in other constituents of the extracellular matrix (e...
April 27, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29700007/abnormal-clotting-of-the-intrinsic-contact-pathway-in-alzheimer-disease-patients-is-related-to-cognitive-ability
#7
Georgette L Suidan, Pradeep K Singh, Sunita Patel-Hett, Zu-Lin Chen, Dmitri Volfson, Hitomi Yamamoto-Imoto, Erin H Norris, Robert D Bell, Sidney Strickland
Alzheimer disease (AD) is a neurodegenerative disorder characterized by extracellular β-amyloid (Aβ) deposition. Although peripheral inflammation and cerebrovascular pathology are reported in AD, there is a lack of plasma biomarkers in this field. Because the contact system is triggered in patient plasma, we hypothesized that the hemostasis profile could be a novel biomarker in AD. Here, we assessed the clotting profile in plasma from AD patients and age-matched controls. Utilizing clinically relevant assays, thromboelastography and activated partial thromboplastin time, we found impaired clot initiation and formation rate in AD patient plasma...
May 8, 2018: Blood Advances
https://www.readbyqxmd.com/read/29619369/cell-receptor-and-cofactor-interactions-of-the-contact-activation-system-and-factor-xi
#8
REVIEW
Monika Pathak, Bubacarr Gibril Kaira, Alexandre Slater, Jonas Emsley
The contact activation system (CAS) or contact pathway is central to the crosstalk between coagulation and inflammation and contributes to diverse disorders affecting the cardiovascular system. CAS initiation contributes to thrombosis but is not required for hemostasis and can trigger plasma coagulation via the intrinsic pathway [through factor XI (FXI)] and inflammation via bradykinin release. Activation of factor XII (FXII) is the principal starting point for the cascade of proteolytic cleavages involving FXI, prekallikrein (PK), and cofactor high molecular weight kininogen (HK) but the precise location and cell receptor interactions controlling these reactions remains unclear...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29587641/the-prevalence-of-heterozygous-f12-mutations-in-chinese-population-and-its-relevance-to-incidents-of-thrombosis
#9
Xi Wu, Qiulan Ding, Xuefeng Wang, Jing Dai, Wenman Wu
BACKGROUND: The contribution of moderate coagulation factor XII (FXII) deficiency to development of thromboembolism is still undetermined. We have tried to show the relevance of FXII deficiency to incidences of venous thrombosis by exploring the prevalence of F12 gene mutations in Chinese patients with thrombotic disorders. METHODS: One hundred and six patients with venous thromboembolism (VTE) and 220 healthy controls were enrolled in study. The coding region and flanking sequences of F12 gene were amplified and sequenced to identify genetic variances...
March 27, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29548426/a-missense-mutation-in-the-plasminogen-gene-within-the-plasminogen-kringle-3-domain-in-hereditary-angioedema-with-normal-c1-inhibitor
#10
Georg Dewald
Hereditary angioedema (HAE) is a genetically heterogeneous disease that is characterized by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. The two classic types, HAE types I and II, are both caused by mutations in the complement C1 inhibitor (SERPING1) gene resulting either in a quantitative or a qualitative deficiency of C1 inhibitor. In so-called HAE type III, in contrast, patients show normal C1 inhibitor measurements in plasma ('HAE with normal C1 inhibitor')...
March 25, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29541637/establishment-of-the-world-health-organization-first-international-standard-for-factor-xii-plasma-human
#11
Helen V Wilmot, Jason Hockley, Peter Rigsby, Elaine Gray
Until recently, the role of factor XII (FXII) in hemostasis was not considered to be important since patients with FXII deficiency do not present with bleeding. The activation of FXII by agents including mast cells and platelet polyphosphates suggests that it may have a role in thrombogenesis. The inhibition of FXII therefore presents an option for antithrombotic therapy, and antibodies and inhibitors are already in development. Assays for FXII will be required to support these technologies, and an international standard (IS) for FXII would be useful for the development of these methods and for the clinical monitoring of patients...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29507382/neutrophil-extracellular-trap-microparticle-complexes-enhance-thrombin-generation-via-the-intrinsic-pathway-of-coagulation-in-mice
#12
Yongzhi Wang, Lingtao Luo, Oscar Ö Braun, Johannes Westman, Raed Madhi, Heiko Herwald, Matthias Mörgelin, Henrik Thorlacius
Abdominal sepsis is associated with dysfunctional hemostasis. Thrombin generation (TG) is a rate-limiting step in systemic coagulation. Neutrophils can expell neutrophil extracellular traps (NETs) and/or microparticles (MPs) although their role in pathological coagulation remains elusive. Cecal ligation and puncture (CLP)-induced TG in vivo was reflected by a reduced capacity of plasma from septic animals to generate thrombin. Depletion of neutrophils increased TG in plasma from CLP mice. Sepsis was associated with increased histone 3 citrullination in neutrophils and plasma levels of cell-free DNA and DNA-histone complexes and administration of DNAse not only eliminated NET formation but also elevated TG in sepsis...
March 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29495652/carbonic-anhydrases-role-in-ph-control-and-cancer
#13
REVIEW
Mam Y Mboge, Brian P Mahon, Robert McKenna, Susan C Frost
The pH of the tumor microenvironment drives the metastatic phenotype and chemotherapeutic resistance of tumors. Understanding the mechanisms underlying this pH-dependent phenomenon will lead to improved drug delivery and allow the identification of new therapeutic targets. This includes an understanding of the role pH plays in primary tumor cells, and the regulatory factors that permit cancer cells to thrive. Over the last decade, carbonic anhydrases (CAs) have been shown to be important mediators of tumor cell pH by modulating the bicarbonate and proton concentrations for cell survival and proliferation...
February 28, 2018: Metabolites
https://www.readbyqxmd.com/read/29483100/coagulation-factor-xii-in-thrombosis-and-inflammation
#14
REVIEW
Coen Maas, Thomas Renné
Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. The factor XII-driven contact system starts coagulation and inflammatory mechanisms via the intrinsic pathway of coagulation and the bradykinin-producing kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood; however, its in vivo functions are just beginning to emerge. Challenging the concept of the coagulation balance, targeting factor XII or its activator polyphosphate, provides protection from thromboembolic diseases without interfering with hemostasis...
April 26, 2018: Blood
https://www.readbyqxmd.com/read/29474926/the-fibrogenic-actions-of-the-coagulant-and-plasminogen-activation-systems-in-pulmonary-fibrosis
#15
REVIEW
Michael Schuliga, Christopher Grainge, Glen Westall, Darryl Knight
Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fibrin formation in the intra-alveolar compartment is postulated to have a pivotal role in the development of pulmonary fibrosis, serving as a provisional matrix for migrating fibroblasts. Furthermore, proteases of the coagulation and plasminogen activation (plasminergic) systems that form and breakdown fibrin respectively directly contribute to pulmonary fibrosis...
April 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29467753/the-plasma-kallikrein-kininogen-pathway-is-critical-in-the-pathogenesis-of-colitis-in-mice
#16
Bo Wang, Aizhen Yang, Zhenzhen Zhao, Chao He, Yuanyuan Liu, Robert W Colman, Jihong Dai, Yi Wu
The kallikrein-kinin system (KKS) consists of two serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-molecular-weight kininogen (HK). Upon activation of the KKS, HK is cleaved to release bradykinin. Although the KKS is activated in humans and animals with inflammatory bowel disease (IBD), its role in the pathogenesis of IBD has not been characterized. In the present study, we determined the role of the KKS in the pathogenesis of IBD using mice that lack proteins involved in the KKS...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29419864/-analysis-of-a-consanguineous-pedigree-affected-with-hereditary-coagulation-factor-xii-deficiency-caused-by-homozygous-gly341arg-mutation
#17
Lihong Yang, Saiyan Jin, Weidan Ji, Xiaoli Cheng, Xiaolong Li, Yanhui Jin, Mingshan Wang
OBJECTIVE To analyze the laboratory phenotype and FXII gene mutation in a consanguineous Chinese pedigree affected with factor XII (FXII) deficiency. METHODS Activated partial thromboplastin time (APTT), FXII activity (FXII:C) and FXII antigen (FXII:Ag) of the proband and her family members (10 individuals from 3 generations) were determined. Sanger sequencing was used to detect potential mutation within the 14 exons, their flanking regions and 5',3'-untranslated regions of the FXII gene. Suspected mutations were verified by backward sequencing...
February 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/29407154/porous-chitosan-microspheres-containing-zinc-ion-for-enhanced-thrombosis-and-hemostasis
#18
Meng Pan, Zonghao Tang, Jianbing Tu, Zhengchao Wang, Qinhui Chen, Rongdong Xiao, Haiqing Liu
Quick hemostats for non-lethal massive traumatic bleeding in battlefield and civilian accidents are important for reducing mortality and medical costs. Chitosan (CS) has been widely used as a clinic hemostat. To enhance its hemostatic efficiency, Zn2+ in the form of zinc alginate (ZnAlg) was introduced to CS to make porous CS@ZnAlg microspheres with ZnAlg component on the surface. Such microspheres were prepared by successive steps of micro-emulsion, polyelectrolyte adhesion, and thermally induced phase separation...
April 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29404650/-coagulation-factors-and-multiple-sclerosis-key-factors-in-the-pathogenesis
#19
REVIEW
K Göbel, C Kleinschnitz, S G Meuth
Environmental factors and genetic predisposition influence the individual risk to develop multiple sclerosis (MS). Preclinical results in animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), prove a significant contribution of the corpuscular and plasmatic coagulation system for the severity of MS. It was recently shown that key molecules of the coagulation cascade, such as fibrinogen, thrombin and factor XII can influence neuroinflammatory disorders such as MS. The inhibition of both fibrinogen and factor XII led to a significantly improved disease course in animal models...
February 5, 2018: Der Nervenarzt
https://www.readbyqxmd.com/read/29393169/hereditary-and-acquired-angioedema-heterogeneity-of-pathogenesis-and-clinical-phenotypes
#20
REVIEW
Maria Bova, Giulia De Feo, Roberta Parente, Tiziana De Pasquale, Carmela Gravante, Stefano Pucci, Eustachio Nettis, Massimo Triggiani
Recurrent angioedema (AE) without wheals is increasingly recognized as a clinical entity and a frequent cause of admission to the emergency room. The Hereditary Angioedema Working Group (HAWK) classification allowed the scientific community to go beyond the semantic confusion that dominated this topic for decades. This classification distinguishes hereditary and acquired forms of AE, either related or unrelated to C1 inhibitor deficiency. Recently, additional mechanisms have been involved in the AE pathogenesis, including the uncontrolled activation of factor XII, generation of vasoactive mediators that induce dysregulation of endothelial functions, and bidirectional interactions between mast cell-derived mediators and the plasma contact system...
2018: International Archives of Allergy and Immunology
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