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Determination of the Structural Changes Accompanying Binding of Protein S to Factor IXa
Conclusion: Based on our preliminary data, we conclude that PS binds strongly with FIXa, and the complex is stabilized by a shift in α-helical content as shown in Figure 1.Figure.1 shows the CD spectral change of PS (curve 1, right panel) due to addition of different concentration of FIXa (curve 2-8, right panel).DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Chatterjee, S., Guidry, J. J., Plautz, W. E., Watt, T., Majumder, R. Tags: 321. Blood Coagulation and Fibrinolytic Factors: Structural Biology of Coagulation Proteins Source Type: research

Regulatory Genetic Variation at the S100B Gene Associates with Vaso-Occlusive Manifestations in Sickle Cell Disease
In sickle cell disease (SCD) polymerization of hemoglobin S under deoxygenated conditions causes vaso-occlusion, which can manifest as acute pain crisis and progressive bone/organ damage. Molecular studies have attributed vaso-occlusion to elevated vascular adhesion and inflammatory responses, whereas the genetic regulation has only recently been assessed.Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) was hybridized to Illumina Human 610-Quad SNP array for the PUSH and Walk-PHaSST cohorts and to Affrymetrix SNP 6.0 array for the Howard SCD expression cohort. Single nucleotide polymorphisms (SNPs) for ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, X., Zhang, W., Saraf, S. L., Nekhai, S., Gladwin, M. T., Machado, R., Gordeuk, V. R. Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster I Source Type: research

The role of calcium handling mechanisms in reperfusion injury.
Abstract Cardiovascular diseases, such as stroke and myocardial infarction (MI) remain the major cause of death and disability worldwide. However, the mortality of MI has declined dramatically over the past several decades because of advances in medicines (thrombolytic agents, antiplatelet drugs, beta blockers, and angiotensin converting enzyme inhibitors) and approaches to restore tissue perfusion(percutaneous coronary intervention and cardiopulmonary bypass). Animals studies have been shown that these treatments have been effective in reducing acute myocardial ischemic injury and limiting MI size. The paradox is...
Source: Current Pharmaceutical Design - November 20, 2018 Category: Drugs & Pharmacology Authors: Pittas K, Vrachatis DA, Angelidis C, Tsoucala S, Giannopoulos G, Defteros S Tags: Curr Pharm Des Source Type: research

Assessment of Non-vitamin K Oral Anticoagulants Use in a Tertiary Care Center in the USA: A Chart Review of 909 Patients
ConclusionA significant number of patients received NOACs at doses inconsistent with the package labeling or had clinically significant drug –drug interactions with NOACs. Efforts are warranted to improve appropriate dosing and avoid significant drug interactions.
Source: American Journal of Cardiovascular Drugs - November 8, 2018 Category: Cardiology Source Type: research

Platelet Signaling in Primary Haemostasis and Arterial Thrombus Formation: Part 1.
Abstract Platelets react immediately in response to traumatic vascular injury by adhesion, activation, aggregation and subsequent haemostatic plug formation. While this reaction pattern is essential for haemostasis, platelet responses can also cause occlusive thrombi in diseased arteries, leading to myocardial infarction or stroke. Initially, flowing platelets are captured from the circulation to vascular lesions. This step is mediated by glycoprotein (GP) Ib-IX-V interacting with immobilized von Willebrand factor (VWF) on exposed subendothelial components. Tethered platelets can now bind to collagen through GPVI ...
Source: Hamostaseologie - October 23, 2018 Category: Hematology Authors: Scharf RE Tags: Hamostaseologie Source Type: research

Gintonin modulates platelet function and inhibits thrombus formation via impaired glycoprotein VI signaling.
In this study, we explored the anti-platelet activity of gintonin (a recently discovered non-saponin fraction of ginseng) against agonist-induced platelet activation. In vitro effects of gintonin on agonist-induced human and rat platelet aggregation, granule secretion, integrin αIIbβ3 activation, and intracellular calcium ion ([Ca2+]i) mobilization were examined. Western blot analysis and immunoprecipitation techniques were used to estimate the expression of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and interaction of glycoprotein VI (GPVI) signaling pathway...
Source: Platelets - June 6, 2018 Category: Hematology Tags: Platelets Source Type: research

Aggregation is impaired in starved platelets due to enhanced autophagy and cellular energy depletion.
Authors: Paul M, Hemshekhar M, Kemparaju K, Girish KS Abstract Platelet hyperactivity is the hallmark of thrombosis and hemostasis disorders including atherosclerosis, diabetes, stroke, arthritis, and cancer causing significant mortality and morbidity. Therefore, regulating platelet hyperactivity is an ever growing interest. Very recently, basal autophagic process has been demonstrated to be essential for normal functioning of platelets. However, autophagy can be elevated above basal level under conditions like starvation, and how platelets respond in these settings remains to be elucidative. Therefore, in this stu...
Source: Platelets - May 30, 2018 Category: Hematology Tags: Platelets Source Type: research

Aortic Root Calcification Score as an Independent Factor for Predicting Major Adverse Cardiac Events in Familial Hypercholesterolemia.
CONCLUSIONS: ARC was significantly associated with future MACE in Japanese patients with heterozygous FH. ARC may start to develop, on average, at 17.4 and 19.7 years of age in males and females, respectively, with heterozygous FH. PMID: 29321389 [PubMed - as supplied by publisher]
Source: Journal of Atherosclerosis and Thrombosis - January 14, 2018 Category: Cardiology Tags: J Atheroscler Thromb Source Type: research

CK2{beta} regulates thrombopoiesis and Ca2+-triggered platelet activation in arterial thrombosis
Platelets, anucleated megakaryocyte (MK)-derived cells, play a major role in hemostasis and arterial thrombosis. Although protein kinase casein kinase 2 (CK2) is readily detected in MKs and platelets, the impact of CK2-dependent signaling on MK/platelet (patho-)physiology has remained elusive. The present study explored the impact of the CK2 regulatory β-subunit on platelet biogenesis and activation. MK/platelet-specific genetic deletion of CK2β (ck2β–/–) in mice resulted in a significant macrothrombocytopenia and an increased extramedullar megakaryopoiesis with an enhanced proportion of prematur...
Source: Blood - December 21, 2017 Category: Hematology Authors: Münzer, P., Walker-Allgaier, B., Geue, S., Langhauser, F., Geuss, E., Stegner, D., Aurbach, K., Semeniak, D., Chatterjee, M., Gonzalez Menendez, I., Märklin, M., Quintanilla-Martinez, L., Salih, H. R., Litchfield, D. W., Buchou, T., Kleins Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research

Effects of Cilnidipine, an L/N-Type Calcium Channel Blocker, on Carotid Atherosclerosis in Japanese Post-Stroke Hypertensive Patients: Results from the CA-ATTEND Study.
CONCLUSIONS: Cilnidipine promoted the regression of common carotid IMT in post-stroke hypertensive patients, especially in the thick group. Cilnidipine also reduced the IAD in both normal and thick groups. PMID: 29225324 [PubMed - as supplied by publisher]
Source: Journal of Atherosclerosis and Thrombosis - December 12, 2017 Category: Cardiology Tags: J Atheroscler Thromb Source Type: research

TRPM7 (Transient Receptor Potential Melastatin-Like 7 Channel) Kinase Controls Calcium Responses in Arterial Thrombosis and Stroke in Mice.
CONCLUSIONS: Our results identify TRPM7 kinase as a key modulator of phospholipase C signaling and store-operated Ca(2+) entry in platelets. The protection of Trpm7(R/R) mice from acute ischemic disease without developing intracranial hemorrhage indicates that TRPM7 kinase might be a promising antithrombotic target. PMID: 29146750 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - November 16, 2017 Category: Cardiology Authors: Gotru SK, Chen W, Kraft P, Becker IC, Wolf K, Stritt S, Zierler S, Hermanns HM, Rao D, Perraud AL, Schmitz C, Zahedi RP, Noy PJ, Tomlinson MG, Dandekar T, Matsushita M, Chubanov V, Gudermann T, Stoll G, Nieswandt B, Braun A Tags: Arterioscler Thromb Vasc Biol Source Type: research

Novel endogenous negative modulators of platelet function as potential anti-thrombotic targets.
Authors: Li YJ, Zhu HX, Zhang D, Li HC, Ma P, Huang LY Abstract Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, g...
Source: European Review for Medical and Pharmacological Sciences - July 27, 2017 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

E-077 Laboratory analogs of challenging thromboemboli in acute ischemic stroke
Conclusion Thrombus analogs with mechanical characteristics similar to those of challenging clinical thrombi were successfully developed. The calcium apatite thrombus analog was found to be stiffer than the fibrin-rich thrombus analog. References . Saver JL et al: Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015, 372(24):2285–2295. . Dorn F et al: Endovascular treatment of acute intracerebral artery occlusions with the solitaire stent: single-centre experience with 108 recanalization procedures. Cerebrovasc Dis 2012, 34(1):70–77. Disclosures: J. Chueh: None. J....
Source: Journal of NeuroInterventional Surgery - July 23, 2017 Category: Neurosurgery Authors: Chueh, J., Litchman, J., Arslanian, R., Carniato, S., Rex, D., Howk, M., Gounis, M., Puri, A. Tags: Electronic Poster Abstracts Source Type: research

Calcified amorphous tumor of the heart with mitral annular calcification: a case report
ConclusionsIn the present case, a calcified amorphous tumor arose from mitral annular calcification. A characteristic of mitral annular calcification-related calcified amorphous tumor is its highly mobile nature, with a high risk of stroke or other systemic embolism. Therefore, surgical therapy should be considered for treatment of calcified amorphous tumors.
Source: Journal of Medical Case Reports - July 18, 2017 Category: General Medicine Source Type: research

New thrombolytic strategy providing neuroprotection in experimental ischemic stroke: MMP10 alone or in combination with tissue-type plasminogen activator
ConclusionThese results show that MMP10, either alone or in combination with tPA, might represent a new strategy for thrombolysis in ischemic stroke, providing higher protection against cerebrovascular damage.
Source: Cardiovascular Research - April 3, 2017 Category: Cardiology Source Type: research

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