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https://www.readbyqxmd.com/read/29355554/dual-inhibition-of-hy023016-based-on-binding-properties-of-platelet-membrane-receptor-subunit-glycoprotein-ib%C3%AE-and-thrombin-exosites
#1
Qiu-Fang Chen, Shuang Cui, Hui-Liang Shen, Xiang Chen, Yun-Zhan Li, Qian Wu, Yun-Gen Xu, Guo-Qing Gong
Thrombin has long been suggested as a desirable antithrombotic target, but anti-thrombin therapy without anti-platelet thereby has never achieved the ideal effect. HY023016 is a novel compound, in our previous study, it exerted better anti-thrombotic than dabigatran etexilate. The present study aims to illustrate the excess anti-thrombotic molecular mechanisms of HY023016 through thrombin anion exosites and the platelet membrane receptor subunit glycoprotein Ibα (GPIbα). HY023016 strongly inhibited the conversion of fibrinogen to fibrous may via blocking thrombin exosite I...
January 17, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29354803/current-advances-in-circulating-inflammatory-biomarkers-in-atherosclerosis-and-related-cardio-cerebrovascular-diseases
#2
Jun-Xuan Lv, Qi Kong, Xin Ma
Atherosclerosis (AS) is a systemic chronic disease affecting both the coronary and cerebral arteries. Inflammation plays a key role in the initiation and progression of AS, and numerous inflammatory factors have been proposed as potential biomarkers. This article reviews recent research in studies on major circulating inflammatory biomarkers to identify surrogates that may reflect processes associated with AS development and the risk of AS-related vascular events, such as Von Willebrand factor, lectin-like oxidized low-density-lipoprotein receptor-1, soluble urokinase plasminogen activator receptor, regulated upon activation, normal T-cell expressed and secreted, and microparticles, which may provide new perspectives for clinical AS evaluation and risk stratification...
December 2017: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/29351342/a-homozygous-missense-variant-in-vwa2-encoding-an-interactor-of-the-fraser-complex-in-a-patient-with-vesicoureteral-reflux
#3
Amelie T van der Ven, Birgit Kobbe, Stefan Kohl, Shirlee Shril, Hans-Martin Pogoda, Thomas Imhof, Hadas Ityel, Asaf Vivante, Jing Chen, Daw-Yang Hwang, Dervla M Connaughton, Nina Mann, Eugen Widmeier, Mary Taglienti, Johanna Magdalena Schmidt, Makiko Nakayama, Prabha Senguttuvan, Selvin Kumar, Velibor Tasic, Elijah O Kehinde, Shrikant M Mane, Richard P Lifton, Neveen Soliman, Weining Lu, Stuart B Bauer, Matthias Hammerschmidt, Raimund Wagener, Friedhelm Hildebrandt
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause (40-50%) of chronic kidney disease (CKD) in children. About 40 monogenic causes of CAKUT have so far been discovered. To date less than 20% of CAKUT cases can be explained by mutations in these 40 genes. To identify additional monogenic causes of CAKUT, we performed whole exome sequencing (WES) and homozygosity mapping (HM) in a patient with CAKUT from Indian origin and consanguineous descent. We identified a homozygous missense mutation (c...
2018: PloS One
https://www.readbyqxmd.com/read/29350417/hepatitis-c-virus-core-protein-induces-dysfunction-of-liver-sinusoidal-endothelial-cell-by-down-regulation-of-silent-information-regulator-1
#4
Li-Jie Sun, Jian-Wu Yu, Yu-Guang Shi, Xiao-Yu Zhang, Meng-Ni Shu, Mo-Yang Chen
Objective Hepatic fibrosis is a frequent feature of chronic hepatitis C virus (HCV) infection. Some evidence has suggested the potential role of silent information regulator 1 (SIRT1) in organ fibrosis. The aim of this study was to investigate the effect of HCV core protein on expression of SIRT1 of liver sinusoidal endothelial cell (LSEC) and function of LSEC. Methods LSECs were co-cultured with HepG2 cells or HepG2 cells expressing HCV core protein and LSECs cultured alone were used as controls. After co-culture, the activity and expression levels of mRNA and protein of SIRT1 in LSEC were detected by a SIRT1 fluorometric assay kit, real time-PCR (RT-PCR), Western blot, respectively...
January 19, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29348121/endothelial-cell-derived-von-willebrand-factor-but-not-platelet-derived-promotes-atherosclerosis-in-apolipoprotein-e-deficient-mice
#5
Prakash Doddapattar, Nirav Dhanesha, Mehul R Chorawala, Chandler Tinsman, Manish Jain, Manasa K Nayak, Janice M Staber, Anil K Chauhan
OBJECTIVE: VWF (von Willebrand factor) is synthesized by endothelial cells and megakaryocytes and is known to contribute to atherosclerosis. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally different from endothelial cell-derived VWF (EC-VWF). We determined the role of different pools of VWF in the pathophysiology of atherosclerosis. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF, EC-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E-deficient (Apoe-/-) background...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29344653/a-novel-variant-of-osteogenesis-imperfecta-type-iv-and-low-serum-phosphorus-level-caused-by-a-val94asp-mutation-in-col1a1
#6
Qi Yang, Hong Xu, Jinsi Luo, Qinle Zhang, Bobo Xie, Sheng Yi, Xiuliang Rong, Jin Wang, Zailong Qin, Tingting Jiang, Li Lin, Yangjin Zuo, Xin Fan
Osteogenesis imperfecta (OI) is a rare congenital disorder characterized by bone fragility and fractures, and associated with bone deformity, short stature, dentin, ligament and blue‑gray eye sclera. OI is caused by a heterozygous mutation in collagen α‑1(I) chain (COL1A1) or collagen α‑2(I) chain (COL1A2) genes that encode α chains of type I collagen. Collagen α chain peptide contains an N‑propeptide, which has a role in assembly and processing of collagen. Point mutations in the N‑propeptide domain appear to trigger OI...
January 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29337416/the-role-of-adamts-13-in-the-coagulopathy-of-sepsis
#7
REVIEW
Marcel Levi, Marie Scully, Mervyn Singer
The interaction between platelets and the vessel wall is mediated by various receptors and adhesive proteins, of which von Willebrand factor is most prominent. The multimeric size of von Willebrand factor is an important determinant of a more intense platelet-vessel wall interaction. and is regulated by the von Willebrand factor cleaving protease, ADAMTS-13. A deficiency in ADAMTS-13 leads to higher concentrations of ultra-large von Willebrand factor multimers and pathological platelet-vessel wall interactions, in its most typical and extreme form leading to thrombocytopenic thrombotic purpura (TTP), a thrombotic microangiopathy characterized by thrombocytopenia, non-immune haemolysis, and organ dysfunction...
January 16, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29337406/validation-of-flow-cytometric-analysis-of-platelet-function-in-patients-with-a-suspected-platelet-function-defect
#8
Ivar van Asten, Roger E G Schutgens, Marije Baaij, Judith Zandstra, Mark Roest, Gerard Pasterkamp, Albert Huisman, Suzanne J A Korporaal, Rolf T Urbanus
BACKGROUND: Light transmission aggregometry (LTA) is the most commonly used test for the diagnosis of platelet function disorders (PFDs), but has moderate sensitivity for mild PFDs. Flow cytometry has been recommended for additional diagnostics of PFDs but is not yet standardized as a diagnostic test. We developed a standardized protocol for flow cytometric analysis of platelet function that measures fibrinogen binding and P-selectin expression as platelet activation markers in response to agonist stimulation...
January 16, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29336529/high-prevalence-of-reduced-thrombin-generation-and-or-decreased-platelet-response-in-women-with-unexplained-heavy-menstrual-bleeding
#9
H P Eising, M Roest, P G de Groot, D Huskens, J Konings, R T Urbanus, B de Laat, J A Remijn
INTRODUCTION: Heavy menstrual bleeding (HMB) is a condition that affects 20%-30% of women of reproductive age. HMB has a multifactorial pathophysiology, which is incompletely understood. HMB symptoms are very common in patients with established haemostasis defects, likewise, women with heavy menstrual bleeding have a higher prevalence of impaired Von Willebrand factor (VWF) levels and function, thrombocytopenia, impaired platelet function and impaired coagulation. The aim of this study was to quantify the prevalence of impaired platelet function, impaired coagulation and reduced VWF activity in patients with HMB...
January 16, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29334682/body-mass-index-and-plasma-p-selectin-before-coronary-stenting-predict-high-residual-platelet-reactivity-at-6-months-on-dual-antiplatelet-therapy
#10
Elena Z Golukhova, Marina V Grigoryan, Mariya N Ryabinina, Naida I Bulaeva, Victor L Serebruany
BACKGROUND: High residual platelet reactivity (HRPR) during dual antiplatelet therapy (DAPT) may impact clinical outcomes following percutaneous coronary interventions (PCI). However, whether any biomarkers assessed before PCI at DAPT loading may predict delayed maintenance HRPR is not clear. OBJECTIVE: The aim of this study was to determine whether conventional clinical or laboratory indices at loading before stenting may predict HRPR at 6 months of maintenance DAPT...
January 16, 2018: Cardiology
https://www.readbyqxmd.com/read/29334169/impact-of-baseline-clinical-and-laboratory-features-on-the-risk-of-thrombosis-in-children-with-acute-lymphoblastic-leukemia-a-prospective-evaluation
#11
Uma H Athale, T Mizrahi, C Laverdière, T Nayiager, Y-L Delva, G Foster, L Thabane, M David, J-M Leclerc, A K C Chan
BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have increased risk of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet uncertain. OBJECTIVE: This exploratory, prospective cohort study evaluated the effects of clinical (age, gender, ALL risk group) and laboratory variables (hematological parameters, ABO blood group, inherited and acquired prothrombotic defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in children (aged 1 to ≤18) treated on the Dana-Farber Cancer Institute ALL 05-001 study...
January 15, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29331958/platelet-secretion-defects-and-acquired-von-willebrand-syndrome-in-patients-with-ventricular-assist-devices
#12
Ulrich Geisen, Kerstin Brehm, Georg Trummer, Michael Berchtold-Herz, Claudia Heilmann, Friedhelm Beyersdorf, Johannes Schelling, Axel Schlagenhauf, Barbara Zieger
BACKGROUND: The number of implanted ventricular assist devices (VADs) has increased significantly recently. Bleeding, the most frequent complication, cannot be solely attributed to anticoagulation therapy. Acquired von Willebrand syndrome (AVWS) caused by increased shear stress is frequent in VAD patients and can increase the bleeding risk. The HeartMate III (HM III) is a novel left VAD featuring potential improvements over the HeartMate II. METHODS AND RESULTS: In this study, we investigated the prevalence and onset of AVWS in 198 VAD patients...
January 13, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29328041/von-willebrand-factor-immunohistochemical-staining-quantitative-optical-density-parameters-in-the-endothelium-and-fibrinoid-of-the-placenta-during-secundines-inflammation-and-concomitant-iron-deficiency-anemia-in-gravidas
#13
V Ilika, I Davydenko
The aim of the research was to set the optical density quantitative parameters of the von Willebrand factor immunohistochemical staining (vWF) in the endothelium and fibrinoid of the placenta during the secundines inflammation concomitant with iron deficiency anemia in gravidas. The total number of 198 placentas was studied. The immunohistochemical technique was performed using the visualization of the primary antibodies to vWF with a diaminobenzidine dye polymer system. The optical density of the histochemical staining was measured by means of computer microdensitometry after the digital copies of the images had been obtained...
December 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29326120/macrophage-scavenger-receptor-sr-ai-contributes-to-the-clearance-of-von-willebrand-factor
#14
Nikolett Wohner, Vincent Muczynski, Amel Mohamadi, Paulette Legendre, Gabriel Aymé, Olivier D Christophe, Peter J Lenting, Cécile V Denis, Caterina Casari
Previously, we identified LDL-receptor related protein-1 on macrophages to mediate shear stress-dependent clearance of von Willebrand factor. In control experiments, however, we observed that von Willebrand factor also binds to macrophages independently of this receptor under static conditions, suggesting the existence of additional clearance-receptors. In search for such receptors, we focused on the macrophage-specific scavenger-receptor SR-AI. Von Willebrand factor displays efficient binding to SR-AI (half-max binding 14+/-5 nM)...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29323038/electroacupuncture-improves-neurovascular-unit-reconstruction-by-promoting-collateral-circulation-and-angiogenesis
#15
Lei Shi, Hong-Mei Cao, Ying Li, Shi-Xin Xu, Yan Zhang, Yang Zhang, Zhe-Feng Jin
Acupuncture at Shuigou (GV26) shows good clinical efficacy for treating stroke, but its mechanism remains poorly understood. In this study, a cerebral infarction model of ischemia/reperfusion injury received electroacupuncture at GV26 (15 Hz and 1 mA, continuous wave [biphasic pulses], for 5 minutes). Electroacupuncture effectively promoted regional cerebral blood flow on the infarct and non-infarct sides, increased infarct lesions, lectin, and number of blood vessels, upregulated von Willebrand factor and cell proliferation marker Ki67 expression, and diminished neurological severity score...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29322496/wt1-peptide-based-immunotherapy-for-advanced-thymic-epithelial-malignancies
#16
Yusuke Oji, Masayoshi Inoue, Yoshito Takeda, Naoki Hosen, Yasushi Shintani, Manabu Kawakami, Takuya Harada, Yui Murakami, Miki Iwai, Mari Fukuda, Sumiyuki Nishida, Jun Nakata, Yoshiki Nakae, Satoshi Takashima, Toshiaki Shirakata, Hiroko Nakajima, Kana Hasegawa, Hiroshi Kida, Takashi Kijima, Soyoko Morimoto, Fumihiro Fujiki, Akihiro Tsuboi, Eiichi Morii, Satoshi Morita, Junichi Sakamoto, Atsushi Kumanogoh, Yoshihiro Oka, Meinoshin Okumura, Haruo Sugiyama
Thymic epithelial tumors are rare malignancies, and no optimal therapeutic regimen has been defined for patients with advanced disease. Patients with advanced thymic epithelial tumors, which were resistant or intolerable to prior therapies, were eligible for this study. Patients received 9 mer-WT1-derived peptide emulsified with Montanide ISA51 adjuvant via intradermal administration once a week as a monotherapy. After the 3 month-protocol treatment, the treatment was continued mostly at intervals of 2 to 4 weeks until disease progression or intolerable adverse events occurred...
January 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29321442/acquired-von-willebrand-syndrome-due-to-aortic-valve-stenosis-in-a-case-with-antiphospholipid-antibody
#17
Hiroaki Tanaka, Yurie Nagai, Chihiro Kuwabara, Ryo Shimizu, Akihide Umeki, Tetsufumi Yamamoto
Acquired von Willebrand syndrome (AVWS) is a bleeding disorder caused by an acquired deficiency of von Willebrand factor (vWF). Some patients with AVWS show a low bleeding tendency and are diagnosed by the presence of a mild prolongation of activated partial thromboplastin time (APTT) preoperatively. Another cause of APTT prolongation is the presence of antiphospholipid antibody (aPL). We experienced a case of AVWS due to aortic valve stenosis in a patient with aPL in whom aortic valve replacement surgery was successful with vWF replacement...
January 11, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29319374/sensitive-and-specific-assessment-of-recombinant-von-willebrand-factor-in-platelet-function-analyzer
#18
Isabell Pekrul, Thorsten Kragh, Peter L Turecek, Aaron R Novack, Helmut W Ott, Michael Spannagl
BACKGROUND: Recombinant von Willebrand factor (rVWF), which was licensed in the United States in 2015, has the multimeric distribution of freshly secreted VWF with ultralarge (UL) and high molecular weight multimers (HMWM) from endothelial cells and megakaryocytes since it has never been exposed to ADAMTS13 or any other proteolytic enzyme. Measurement of closure time (CT) using the platelet function analyzer-200 (PFA-200) is highly sensitive to the presence of UL VWF multimers in added VWF concentrates...
January 10, 2018: Platelets
https://www.readbyqxmd.com/read/29317405/coagulation-and-fibrinolysis-in-hyperparathyroidism-secondary-to-vitamin-d-deficiency
#19
Laura P B Elbers, Marije Wijnberge, Joost C M Meijers, Dennis C W Poland, Dees P M Brandjes, Eric Fliers, Victor E A Gerdes
INTRODUCTION: Abnormal coagulation tests have been observed in patients with primary hyperparathyroidism (HPT) suggesting a prothrombotic effect of parathyroid hormone (PTH). Vitamin D deficiency (VIDD) is the most frequent cause of secondary HPT. Aim of our study was to investigate the influence of HPT secondary to moderate-severe VIDD and vitamin D replacement on the coagulation and fibrinolysis system. SUBJECTS AND METHODS: Prospective cohort study of patients with vitamin D<25 nmol/l with and without HPT, and a control group of patients on vitamin D suppletion...
January 9, 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29315844/local-and-systemic-coagulation-marker-response-to-musculocutaneous-flap-ischemia-reperfusion-injury-and-remote-ischemic-conditioning-an-experimental-study-in-a-porcine-model
#20
Andreas Engel Krag, Christine Lodberg Hvas, Birgitte Jul Kiil, Gete Toft Eschen, Tine Engberg Damsgaard, Anne-Mette Hvas
BACKGROUND: Remote ischemic conditioning (RIC) administered by non-lethal periods of extremity ischemia and reperfusion attenuates ischemia-reperfusion injury. We aimed to investigate the local and systemic coagulation marker response to flap ischemia-reperfusion injury, and the effects of RIC on coagulation markers following flap ischemia-reperfusion injury. METHODS: A musculocutaneous latissimus dorsi flap was subjected to 4 h of ischemia followed by 7 h of reperfusion in 16 female Danish Landrace pigs (39 kg)...
January 8, 2018: Microsurgery
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