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Multiplexed digital quantification of binge-like alcohol-mediated alterations in maternal uterine angiogenic mRNA transcriptome.

Genomic studies on fetal alcohol spectrum disorders (FASD) have utilized either genome-wide microarrays/bioinformatics or targeted real-time PCR (RT-PCR). We utilized herein for the first time a novel digital approach with high throughput as well as the capability to focus on one physiological system. The aim of the present study was to investigate alcohol-induced alterations in uterine angiogenesis-related mRNA abundance using digital mRNA technology. Four biological and three technical replicates of uterine arterial endothelial cells from third-trimester ewes were fluorescence-activated cell

Binding site on human von Willebrand factor of bitiscetin, a snake venom-derived platelet aggregation inducer.

Bitiscetin, a C-type lectin-like heterodimeric snake venom protein purified from Bitis arietans, binds to human von Willebrand factor (VWF) and induces the platelet membrane glycoprotein (GP) Ib-dependent platelet agglutination in vitro similar to botrocetin. In contrast with botrocetin which binds to the A1 domain of VWF, the A3 domain, a major collagen-binding site of VWF, was proposed to be a bitiscetin-binding site. In the competitive binding assay, neither bitiscetin nor botrocetin had an inhibitory effect on the VWF binding to the immobilized type III collagen on a plastic plate. The ant

Coagulation, fibrinolytic system activation and endothelial dysfunction in patients with mitral stenosis and sinus rhythm.

Anticoagulation treatment can prevent systemic embolism in patients with mitral stenosis (MS) and atrial fibrillation (AF), but this treatment is under debate if patients are in sinus rhythm. The authors aimed to determine the hemostatic changes in patients with MS and sinus rhythm. Forty-six patients (28 in sinus rhythm and 18 in AF) with mitral stenosis were enrolled in this study. They studied systemic venous fibrinogen, D-dimer, antithrombin-III, tissue plasminogen activator (tPA), plasminogen activator inhibitor-I (PAI-I), von Willebrand factor (vWF), and platelet factor 4 (PF 4) in these…

Частота проведения позитивных тестов на антиPF4/polianion антител после вакцинации COVID-19 с помощью CADOx1 nCOV-19 и BNT162b2.

Вакцинация с использованием аденовального вектора COVID-19 вакцины ChADOx1 nCOV-19 (AstraZeneca) была связана с редкой иммунной тромботической тромбоцитопенией (VITT). Затрагиваемые пациенты испытывают сильно положительный коэффициент по тромбоцитам 4 (PF4)/полианионическим ферментам иммуномассы (ОВОС), а активация тромбоцитов, вызванная сывороткой, является максимальной в присутствии PF4. Мы определили частотность антиPF4/polianion антител в здоровых вакцинах и оценили, обнаруживают ли PF4/polianion EIA+ serа-активирующие свойства после вакцинации с помощью CADOx1 nCOV-19 (n = 138) или BNT162

Совпадение в аннотации оригинала
Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in platelet factor 4 (PF4)/polyanion enzyme immunoassays (EIAs), and serum-induced platelet activation is maximal in the presence of PF4. We de…

A cluster of pediatric vaccine-induced immune thrombotic thrombocytopenia-like cases with thrombosis and thrombocytopenia following respiratory infections-case series.

BACKGROUND: Adenoviral vector COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is a heparin-independent platelet-activatin … d syndrome. Heterozygosity for factor V Leiden was found in 2 children. In 2 patients for whom anti-platelet factor 4 (PF4) serology was performed, positive results were found by PF4/polyanion lateral-flow immunoassay but negative results by PF4/polyanion chemiluminescence immunoassay. All patients were treated with enoxaparin or fondaparinux and intravenous immuno …

An Increase in Mean Platelet Volume/Platelet Count Ratio Is Associated with Vascular Access Failure in Hemodialysis Patients.

After stenosis of arteriovenous vascular access in hemodialysis patients, platelets play a crucial role in subsequent thrombus formation, leading to access failure. In a previous study, the mean platelet volume (MPV)/platelet count ratio, but not MPV alone, was shown to be an independent predictor of 4-year mortality after myocardial infarction. However, little is known about the potential influence of MPV/platelet count ratio on vascular access patency in hemodialysis patients. A total of 143 patients undergoing routine hemodialysis were recruited between January 2013 and February 2016. Vascu

Measurement of soluble C-type lectin-like receptor 2 in human plasma.

Detection of platelet activation in vivo is useful to identify patients at risk of thrombotic diseases. Platelet factor 4 (PF4) and β-thromboglobulin (β-TG) are used for this purpose; however, they are easily released upon the minimal platelet activation that occurs during sampling. Soluble forms of several platelet membrane proteins are released upon platelet activation; however, the soluble form of C-type lectin-like receptor 2 (sCLEC-2) has not yet been fully investigated. Western blotting with an anti-CLEC-2 antibody showed that sCLEC-2 was released from washed human platelets stimulated w…

Platelet-derived growth factor inhibition--a new treatment of pulmonary hypertension in congenital diaphragmatic hernia?

Increased pulmonary vascular resistance causing pulmonary artery hypertension is a major problem in the treatment of congenital diaphragmatic hernia with a strong association to mortality. We here report a patient with intractable pulmonary hypertension at 4 weeks of age unresponsive to conventional treatment. After administration of the platelet-derived growth factor (PDGF) receptor antagonist imatinib, pulmonary artery pressure gradually decreased to acceptable levels and the patient's clinical condition gradually improved.

Lineage-specific overexpression of the P2Y1 receptor induces platelet hyper-reactivity in transgenic mice.

In order to investigate the role of the platelet P2Y1 receptor in several aspects of platelet activation and thrombosis, transgenic (TG) mice overexpressing this receptor specifically in the megakaryocytic/platelet lineage were generated using the promoter of the tissue-specific platelet factor 4 gene. Studies of the saturation binding of [33P]2MeSADP in the presence or absence of the selective P2Y1 antagonist MRS2179 indicated that wild-type (WT) mouse platelets bore 150 +/- 31 P2Y1 receptors and TG platelets 276 +/- 34, representing an 84% increase in P2Y1 receptor density. This led to a wel…

Efficacy of helicobacter pylori eradication as an upfront treatment of secondary immune thrombocytopenia: an experience from Pakistan.

BACKGROUND: The effect of Helicobacter-pylori eradication therapy on the platelet counts in patients with immune thrombocytopenia is still debatable. The aim of this study was to assess the response rates of standard triple eradication therapy in secondary immune thrombocytopenia with Helicobacter pylori infection. METHODS: From January 2012 to December 2013, 197 patients were diagnosed to have immune thrombocytopenia, out of which 22(11.1%) patients infected with Helicobacter- Pylorus were enrolled in this study. Helicobacter-Pylori infection was documented by Helicobacter-pylori stool antig

[Thrombocytopenia induced by type II heparin and myocardial infarct: 2 case reports].

Heparin-induced thrombocytopenia (HIT) type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometim…

Platelet-activating histone/antihistone IgG complexes in anti-PF4-negative thrombosis and thrombocytopenia syndrome.

Thrombosis and thrombocytopenia syndromes (TTS) describe immune-mediated thrombotic adverse reactions after vaccination against COVID-19. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a well-known subentity of TTS, caused by adenovirus vector-based vaccines. VITT is mediated by anti-platelet factor 4 (PF4) immunoglobulin G (IgG) antibodies, activating platelets via Fc-γ IIa receptors (FcγRIIa). We describe clinical and serological features of 18 patients with anti-PF4/heparin enzyme-linked immunosorbent assay (ELISA)-negative TTS in temporal relationship to messenger RNA (mRNA)-…

The effects of platelet-rich plasma on hypertrophic scars fibroblasts.

We hypothesised that a feedback mechanism of the transforming growth factor (TGF)-β1 signalling pathway, triggered by high-level TGF-β1, activates platelet-rich plasma (PRP) release to reduce connective tissue growth factor (CTGF) production and expression of CTGF mRNA in hypertrophic scar dermal fibroblasts. Primary dermal fibroblasts were isolated from cultures of hypertrophic scars. Cells were cultured after addition of serum-free Dulbecco's modified Eagle's medium supplemented with 5% (wt/vol) PRP or platelet-poor plasma (PPP). At 1, 4, 6, 8, 11, and 13 days after addition of PRP or PPP, t

Low-grade endotoxemia and platelet activation in cirrhosis.

UNLABELLED: Patients with cirrhosis may display impaired or enhanced platelet activation, but the reasons for these equivocal findings are unclear. We investigated if bacterial lipopolysaccharide (LPS) is implicated in platelet activation. In a cross-sectional study, conducted in an ambulatory care clinic and hospital, comparing 69 cirrhosis patients and 30 controls matched for sex, age, and atherosclerotic risk factors, serum levels of LPS, soluble cluster of differentiation 40 ligand and p-selectin (two markers of platelet activation), and zonulin (a marker of gut permeability) were investig

Impaired expression of the thrombopoietin receptor by platelets from patients with polycythemia vera.

BACKGROUND: The cause of polycythemia vera, which originates from a multipotent hematopoietic progenitor cell, is unknown. Thrombopoietin is a hematopoietic growth factor that regulates the production of multipotent hematopoietic progenitor cells and platelets. To evaluate the possibility that an abnormality in thrombopoietin-mediated signal transduction might be involved in the pathogenesis of polycythemia vera, we examined thrombopoietin-induced tyrosine phosphorylation of proteins and the expression of the thrombopoietin receptor in platelets from patients with the disease. METHODS: Platel

Platelet-released growth factors promote pro-angiogenic effects in endothelial cells: a translational perspective on wound healing and regenerative medicine.

Platelet-Released Growth Factors (PRGF) are a standardized, cell- and fibrin-free platelet lysate with translational potential for tissue re … esis-related genes and increased signals of representative angiogenesis-associated mediators (e.g., Platelet Factor 4, Angiopoietin-1, Angiogenin) following PRGF stimulation. Functional tube formation assays demonstrated significant enhancement of multiple pro-angiogenic parameters in response to PRGF, including number of pieces (P < 0.001), junctions (P < 0.01), a …

Translational immunothrombosis in autoimmune Heparin-Induced thrombocytopenia: targeting the FcγRIIa-Syk-BTK and complement pathways.

Autoimmune heparin-induced thrombocytopenia (aHIT) represents a severe variant of immune-mediated thrombocytopenias (IMTs) in which anti-platelet factor 4 (PF4) antibodies activate platelets independently of heparin, leading to both thrombosis and thrombocytopenia. Despite its clinical significance, aHIT remains poorly understood and lacks evidence-based immunomodulatory treatments. This narrative translational review integrates mechanistic and therapeutic insights from immune thrombocytopenia (ITP) and antiphospholipid syndrome (APS) to identify shared pathogenic pathways relevant to aHIT. Li…

Explaining COVID-19 postvaccination-related immune thrombotic thrombocytopenia: a hypothesis-generating in-silico approach.

Cases that experienced COVID-19 postvaccination-related thrombosis have been reported after the first dose of ChAdOx1 nCov-19 (Vaxzevria, AstraZeneca) or Ad26.COV2.S (Johnson & Johnson/Janssen) vaccine. These rare thrombotic events were observed within the expected vaccine-induced seroconversion period and could be attributed to platelet-activating (auto)antibodies against platelet factor 4 (PF4). Newly, vaccine-induced, cross-reactive anti-PF4 antibodies could explain this observation. An in-silico analysis using the Basic Local Alignment Search Tool was used to identify sequence similarity b…

Serotonin-release assay-negative heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Pathogenic HIT antibodies can be detected by the serotonin-release assay (SRA), a platelet activation test. We have regarded the SRA performed in our medical community ("McMaster" SRA) as having high sensitivity and specificity. Recently, the concept of "SRA-negative HIT" has been proposed for enzyme-immunoassay (EIA)-positive/SRA-negative patients with a HIT-compatible clinical picture, who test positive in a PF4-enhanced platelet activation as…

Stage-dependent association of BDNF and TGF-β1 with lung function in stable COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterised by complex inflammatory, neuronal and fibrotic changes. Brain-derived Neurotrophic Factor (BDNF) is a key regulator of neuronal plasticity, whereas Transforming Growth Factor-β1 (TGF-β1) plays a crucial role in tissue repair and emphysema pathogenesis. Both mediators are stored in platelets and released from platelets in inflammatory conditions and during serum preparation. In patients with asthma, it was previously shown that elevated serum BDNF concentrations correlate with disease severity, whereas TGF-β1 concentratio