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https://www.readbyqxmd.com/read/28453888/live-imaging-of-extracellular-signal-regulated-kinase-and-protein-kinase-a-activities-during-thrombus-formation-in-mice-expressing-biosensors-based-on-f%C3%A3-rster-resonance-energy-transfer
#1
Takuya Hiratsuka, Takeshi Sano, Hisashi Kato, Naoki Komatsu, Masamichi Imajo, Yuji Kamioka, Kenta Sumiyama, Fumiaki Banno, Toshiyuki Miyata, Michiyuki Matsuda
BACKGROUND: Dynamic features of thrombus formation have been visualized by conventional video wide field microscopy or confocal microscopy in live mouse. However, due to technical limitations precise spatiotemporal regulation of intracellular signaling molecule activities, which have been extensively studied in vitro, remains elusive in vivo. OBJECTIVES: By two-photon excitation microscopy of transgenic mice expressing Förster resonance energy transfer (FRET) biosensors for extracellular signal-regulated kinase (ERK) and protein kinase A (PKA), we visualized ERK and PKA activities during thrombus formation in laser-injured subcutaneous arterioles RESULTS: When a core of densely packed platelets was developed, ERK activity was increased from the basal region close to the injured arterioles...
April 28, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28448438/antiplatelet-activity-of-a-newly-synthesized-novel-ruthenium-ii-a-potential-role-for-akt-jnk-signaling
#2
Themmila Khamrang, Kuo-Chen Hung, Chih-Hsuan Hsia, Cheng-Ying Hsieh, Marappan Velusamy, Thanasekaran Jayakumar, Joen-Rong Sheu
In oncotherapy, ruthenium complexes are considered as potential alternatives for platinum compounds, and have been proved as promising anticancer drugs with high efficacy and lesser side effects. Platelet activation plays a major role in cancer metastasis and progression. Hence, this study explored the effect of a newly synthesized ruthenium complex, [Ru(η⁶-cymene)(L)Cl]BF₄(TQ5), where L = 4-phenyl-2-pyridin-2-yl-quinazoline), on human platelet activation. TQ5 (3-5 µM) inhibited concentration-dependent collagen-induced platelet aggregation in washed human platelets...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28446591/nfat5-sensitive-orai1-expression-and-store-operated-ca-2-entry-in-megakaryocytes
#3
Itishri Sahu, Lisann Pelzl, Basma Sukkar, Hajar Fakhri, Tamer Al-Maghout, Hang Cao, Stefan Hauser, Ravi Gutti, Meinrad Gawaz, Florian Lang
The transcription factor NFAT5 is up-regulated in several clinical disorders including dehydration. NFAT5-sensitive genes include serum and glucocorticoid-inducible kinase (SGK)-1. The kinase is a powerful regulator of Orai1, a Ca(2+)-channel accomplishing store-operated Ca(2+)-entry (SOCE). Orai1 is stimulated after intracellular store depletion by the Ca(2+) sensors stromal interaction molecule (STIM)-1, or STIM2, or both. In the present study, we explored whether nuclear factor of activated T cell (NFAT)-5 influences Ca(2+)-signaling in megakaryocytes...
April 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#4
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28439930/detection-and-identification-of-platelet-antibodies-using-a-sensitive-multiplex-assay-system-platelet-antibody-bead-array
#5
Krista Metzner, Julie Bauer, Heather Ponzi, Allison Ujcich, Brian R Curtis
BACKGROUND: Tests for platelet-specific antibodies are important in the diagnosis of immune platelet disorders. Monoclonal antibody glycoprotein capture assays have been the gold standards in platelet antibody detection for almost 30 years. However, such assays are complex and cumbersome to perform, which limits their routine use. We report the performance of a newly developed, easy to perform platelet antibody bead array (PABA) for the detection of platelet-specific antibodies. STUDY DESIGN AND METHODS: PABA is the equivalent of the monoclonal antigen capture enzyme-linked immunosorbent assay (ELISA) (MACE) on a bead and instead with fluorescent detection of immunoglobulin (Ig)G platelet antibodies by Luminex...
April 25, 2017: Transfusion
https://www.readbyqxmd.com/read/28436749/differential-diagnosis-of-neonatal-alloimmune-thrombocytopenia-type-2b-von-willebrand-disease
#6
Mathilde Penel-Page, Sandrine Meunier, Mathilde Fretigny, Sandra Le Quellec, Pierre Boisseau, Christine Vinciguerra, Catherine Ternisien, Lucia Rugeri
At birth, severe thrombocytopenia without context of infection should mainly suggest neonatal alloimmune thrombocytopenia (NAIT), especially in case of a platelet count below 20 GL(-1). We report two cases of severe neonatal thrombocytopenia, first suspected as being NAIT. Both had a platelet count below 20 GL(-1) with platelet clumps. The absence of alloantibodies and failure of platelet transfusion and intravenous immunoglobulins to improve the platelet count led to question the diagnosis and to evoke inherited bleeding disorders...
April 24, 2017: Platelets
https://www.readbyqxmd.com/read/28435982/-changes-in-biological-functions-of-high-density-lipoprotein-after-abnormal-modification
#7
Hang Qu, Yang Yu, Shu-Cun Qin, Guo-Hua Song
High-density lipoprotein (HDL) is composed of apolipoproteins, lipids and functional proteins. HDL protects against atherosclerosis (AS) by reverse cholesterol transport (RCT). HDL inhibits the lipid oxidation, inflammation and restores endothelial function. During systemic inflammation or metabolic disorders, HDL can be modified abnormally and converted to a dysfunctional type, which results in the loss of anti-inflammatory factors including apolipoprotein A-I (apoA-I), paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH), and gains of pro-inflammatory factors such as serum amyloid A (SAA), triglyceride (TG) and oxidative lipid...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28435309/recognition-and-management-of-platelet-refractory-bleeding-in-patients-with-glanzmann-s-thrombasthenia-and-other-severe-platelet-function-disorders
#8
Meera Chitlur, Madhvi Rajpurkar, Michael Recht, Michael D Tarantino, Donald L Yee, David L Cooper, Sriya Gunawardena
Patients with rare qualitative platelet disorders or platelet function disorders (PFDs) may present to the hospital physician with severe bleeding episodes or excessive surgical bleeding. Although standard treatment consists of platelet transfusions, repeated transfusions may result in the development of antiplatelet antibodies (APA) or clinical refractoriness, rendering further platelet therapy ineffective. In such settings, an approved treatment option for patients with Glanzmann's thrombasthenia (GT), one of the well-known rare PFDs, is recombinant activated coagulation factor VII (rFVIIa)...
2017: International Journal of General Medicine
https://www.readbyqxmd.com/read/28435120/the-role-of-platelets-in-hemostasis-and-the-effects-of-snake-venom-toxins-on-platelet-function
#9
REVIEW
Mayara Ribeiro de Queiroz, Bruna Barbosa de Sousa, Déborah Fernanda da Cunha Pereira, Carla Cristine Neves Mamede, Mariana Santos Matias, Nadia Cristina Gomes de Morais, Júnia de Oliveira Costa, Fábio de Oliveira
The human body has a set of physiological processes, known as hemostasis, which keeps the blood fluid and free of clots in normal vessels; in the case of vascular injury, this process induces the local formation of a hemostatic plug, preventing hemorrhage. The hemostatic system in humans presents complex physiological interactions that involve platelets, plasma proteins, endothelial and subendothelial structures. Disequilibrium in the regulatory mechanisms that control the growth and the size of the thrombus is one of the factors that favors the development of diseases related to vascular disorders such as myocardial infarction and stroke, which are among the leading causes of death in the western world...
April 20, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28434090/a-best-practice-position-statement-on-the-role-of-the-nephrologist-in-the-prevention-and-follow-up-of-preeclampsia-the-italian-study-group-on-kidney-and-pregnancy
#10
Giorgina Barbara Piccoli, Gianfranca Cabiddu, Santina Castellino, Giuseppe Gernone, Domenico Santoro, Gabriella Moroni, Donatella Spotti, Franca Giacchino, Rossella Attini, Monica Limardo, Stefania Maxia, Antioco Fois, Linda Gammaro, Tullia Todros
Preeclampsia (PE) is a protean syndrome causing a transitory kidney disease, characterised by hypertension and proteinuria, ultimately reversible after delivery. Its prevalence is variously estimated, from 3 to 5% to 10% if all the related disorders, including also pregnancy-induced hypertension (PIH) and HELLP syndrome (haemolysis, increase in liver enzyme, low platelets) are included. Both nephrologists and obstetricians are involved in the management of the disease, according to different protocols, and the clinical management, as well as the role for each specialty, differs worldwide...
April 22, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28433984/haemophagocytic-lymphohistiocytosis-presenting-as-hellp-syndrome-a-diagnostic-and-therapeutic-challenge
#11
Robert Noel Kerley, Raymond Michael Kelly, Mary Rose Cahill, Louise Clare Kenny
Haemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal, haematological disorder, which can be clinically challenging to diagnose and manage. We report a case of HLH in a previously healthy 33-year-old primigravida. The patient presented at 22 weeks gestation with dyspnoea, abdominal pain, anaemia, thrombocytopenia and elevated liver enzymes suggestive of HELLP syndrome.HELLP, a syndrome characterised by haemolysis, elevated liver enzymes and low platelets is considered a severe form of pre-eclampsia...
April 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28433569/vitamin-d-binding-protein-rs7041-polymorphism-and-high-residual-platelet-reactivity-in-patients-receiving-dual-antiplatelet-therapy-with-clopidogrel-or-ticagrelor
#12
Monica Verdoia, Veronica Daffara, Patrizia Pergolini, Roberta Rolla, Paolo Marino, Giorgio Bellomo, Alessandro Carriero, Giuseppe De Luca
BACKGROUND: Vitamin D deficiency represents a major health problem in general population, especially for its association with cardiovascular disorders and thrombotic risk, even in patients on dual antiplatelet therapy (DAPT). Vitamin D Binding Protein (VDBP) is the main transporter of vitamin D in the bloodstream and genetic polymorphisms of this protein have been shown to account for a significant variability of vitamin D levels and its systemic effects. Contrasting data have linked the rs7041 T→G substitution with cardiovascular disease...
April 19, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28432223/fli1-level-during-megakaryopoiesis-affects-thrombopoiesis-and-platelet-biology
#13
Karen K Vo, Danuta J Jarocha, Randolph B Lyde, Vincent Hayes, Christopher S Thom, Spencer K Sullivan, Deborah L French, Mortimer Poncz
Friend Leukemia Virus Integration 1 (FLI1), a critical transcription factor (TF) during megakaryocyte differentiation, is amongst genes hemizygously deleted in Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau syndrome (PTSx). Recently, heterozygote human FLI1 mutations have been ascribed to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand these clinical disorders, beginning with iPSCs generated from a PTSx patient and iPSCs from a control line with a targeted heterozygous FLI1 knockout (FLI1(+/-))...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28431870/the-effect-of-hypertonic-saline-and-mannitol-on-coagulation-in-moderate-traumatic-brain-injury-patients
#14
Haifeng Wang, Hongshi Cao, Xiaohong Zhang, Liang Ge, Li Bie
BACKGROUND: Hyperosmolar therapy, using either hypertonic saline (HTS) or mannitol (MT), is considered the treatment of choice for intracranial hypertension, a disorder characterized by high intracranial pressure (ICP). However, hyperosmolar agents have been postulated to impair coagulation and platelet function. The aim of this study was to identify whether HTS and MT could affect coagulation in moderate traumatic brain injury (TBI) patients. METHODS: In this prospective and randomized double-blind study, we included adult patients with moderate TBI...
April 14, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28431186/unfractionated-heparin-versus-low-molecular-weight-heparins-for-avoiding-heparin-induced-thrombocytopenia-in-postoperative-patients
#15
REVIEW
Daniela R Junqueira, Liliane M Zorzela, Edson Perini
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28428218/gain-of-function-mutation-in-filamin-a-potentiates-platelet-integrin-%C3%AE-iib%C3%AE-3-activation
#16
Eliane Berrou, Frédéric Adam, Marilyne Lebret, Virginie Planche, Patricia Fergelot, Odile Issertial, Isabelle Coupry, Jean-Claude Bordet, Paquita Nurden, Dominique Bonneau, Estelle Colin, Cyril Goizet, Jean-Philippe Rosa, Marijke Bryckaert
OBJECTIVE: Dominant mutations of the X-linked filamin A (FLNA) gene are responsible for filaminopathies A, which are rare disorders including brain periventricular nodular heterotopia, congenital intestinal pseudo-obstruction, cardiac valves or skeleton malformations, and often macrothrombocytopenia. APPROACH AND RESULTS: We studied a male patient with periventricular nodular heterotopia and congenital intestinal pseudo-obstruction, his unique X-linked FLNA allele carrying a stop codon mutation resulting in a 100-amino acid-long FLNa C-terminal extension (NP_001447...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28427942/inhibitory-effects-of-ethyl-pyruvate-on-platelet-aggregation-and-phosphatidylserine-exposure
#17
Wenjin Li, Xinyu Yang, Minyuan Peng, Can Li, Guangfu Mu, Fangping Chen
Ethyl pyruvate (EP) is a stable lipophilic pyruvate derivative. Studies demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti-coagulant effects. Inflammation and coagulation are closely interacted with platelet activation. However, it is unclear whether EP has anti-platelet effects. Therefore, we investigated the anti-platelet effect of EP in this study in vitro. We found that EP inhibited agonists induced platelets aggregation, ATP release and adhesion to collagen. Flow cytometric analysis revealed that EP inhibited agonist induced platelets PAC-1 binding, as well as P-selectin and CD40L expression...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28427477/plasma-chitotriosidase-activity-versus-ccl18-level-for-assessing-type-i-gaucher-disease-severity-protocol-for-a-systematic-review-with-meta-analysis-of-individual-participant-data
#18
Tatiana Raskovalova, Patrick B Deegan, Ruby Yang, Elena Pavlova, Jérome Stirnemann, José Labarère, Ari Zimran, Pramod K Mistry, Marc Berger
BACKGROUND: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by deficiency in acid beta-glucosidase. GD exhibits a wide clinical spectrum of disease severity with an unpredictable natural course. Plasma chitotriosidase activity and CC chemokine ligand 18 (CCL18) have been exchangeably used for monitoring GD activity and response to enzyme replacement therapy in conjunction with clinical assessment. Yet, a large-scale head-to-head comparison of these two biomarkers is currently lacking...
April 20, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28427446/respiratory-chain-complex-iii-deficiency-due-to-mutated-bcs1l-a-novel-phenotype-with-encephalomyopathy-partially-phenocopied-in-a-bcs1l-mutant-mouse-model
#19
Saara Tegelberg, Nikica Tomašić, Jukka Kallijärvi, Janne Purhonen, Eskil Elmér, Eva Lindberg, David Gisselsson Nord, Maria Soller, Nicole Lesko, Anna Wedell, Helene Bruhn, Christoph Freyer, Henrik Stranneheim, Rolf Wibom, Inger Nennesmo, Anna Wredenberg, Erik A Eklund, Vineta Fellman
BACKGROUND: Mitochondrial diseases due to defective respiratory chain complex III (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is completed by the insertion of the Rieske iron-sulfur protein, a process for which BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising from mutations in this gene is wide. RESULTS: A case of CIII deficiency was investigated in depth to assess respiratory chain function and assembly, and brain, skeletal muscle and liver histology...
April 20, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28427432/anti-human-platelet-antigen-hpa-1a-antibodies-may-affect-trophoblast-functions-crucial-for-placental-development-a-laboratory-study-using-an-in-vitro-model
#20
Mariana Eksteen, Gøril Heide, Heidi Tiller, Yan Zhou, Nora Hersoug Nedberg, Inigo Martinez-Zubiaurre, Anne Husebekk, Bjørn R Skogen, Tor B Stuge, Mette Kjær
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by maternal antibodies against paternal human platelet antigens (HPAs) on fetal platelets. Antibodies against HPA-1a are accountable for the majority of FNAIT cases. We have previously shown that high levels of maternal anti-HPA-1a antibodies are associated with clinically significant reduced birth weight in newborn boys. Chronic inflammatory placental lesions are associated with increased risk of reduced birth weight and have previously been reported in connection with FNAIT pregnancies...
April 21, 2017: Reproductive Biology and Endocrinology: RB&E
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