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Stress depended changes in activityof gp red blood cells receptors and its correction by therahertz waves at nitric oxide frequency  [PDF]
Kirichuk V.F.,Svistunov S.V.,Andronov E.V.,Ivanov A.N.
Saratov Journal of Medical Scientific Research , 2011,
Abstract: The effect of electromagnetic radiation in the terahertz range frequencies of molecular spectrum of emission and absorption of nitric oxide 150.176–150.664 GHz for the restoration of the impaired carbohydrate component and functional activity glikoproteid receptors of erythrocytes of white rats in a state of acute imm obilization stress. Shown that exposure to electromagnetic waves at these frequencies is the normalization of the increased content of b-D-galactose in the carbohydrate component and the restoration of the impaired activity of the receptors glikoproteid erythrocytes
Bull spermatozoa express receptors for platelet-activating factor
Bosch,Pablo; Roudebush,William E; McGraw,Royal A; Mel DeJarnette,J; Marshall,Clifton E; Massey,Joe B; Brackett,Benjamin G;
Revista Científica , 2009,
Abstract: platelet-activating factor (paf; 1-o-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a ubiquitous phospholipid that is implicated in the mediation of a wide variety of reproductive processes. to better understand the role of paf in bovine reproduction, it was designed experiments to: (a) determine whether bull spermatozoa express receptors for paf and (b) study the effect of exogenous paf on in vitro sperm physiology (i.e., capacitation, acrosome reaction, motility, and fertilizing ability). bull sperm express paf receptor as determined by two approaches: rt-pcr and immunofluorescence. however, exposure of spermatozoa to different concentrations of exogenous paf (10-11-10-6 m) did not affect capacitation, acrosome reaction or motility. consistent with these findings, coculture of gametes in medium containing increasing concentrations of paf (1 x 10-8-8 x 10-6 m) did not improve in vitro fertilization outcome as measured by percentage of inseminated oocytes reaching 2-cell stage 48 h after fertilization. in contrast, paf at 8 x 10-6 m concentration significantly inhibited ivf. in conclusion, although bull sperm have paf receptors, exposure of bull spermatozoa to exogenous paf failed to enhance the sperm function parameters measured in this study. additional studies are warranted to elucidate the biological role of paf on bull spermatozoa.
Possible Role of Platelet GluR1 Receptors in Comorbid Depression and Cardiovascular Disease  [PDF]
Hu Chen
Cardiovascular Psychiatry and Neurology , 2009, DOI: 10.1155/2009/424728
Abstract: The exact nature of the comorbidity between cardiovascular disease (CVD) and major depressive disorder (MDD) is poorly understood. The proposed mechanisms include various biochemical and molecular pathways as well as health behaviors such as physical inactivity. One possible link between MDD and CVD is increased platelet activity and blood viscosity. Recently, it was discovered that platelets express functional subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, for example, glutamate receptor 1 (GluR1). Here, I propose that this type of AMPA receptor could play a role in comorbid MDD and CVD, and antidepressants may interfere with platelet activation via direct or indirect effects on platelet GluR1 phosphorylation. Testing this hypothesis could provide a novel view on the pathobiological mechanisms of comorbid MDD and CVD. With respect to the recently discovered role of AMPA receptors in regulating platelet activation and thrombosis, it appears that the information about the putative effects of psychoactive AMPA-modifying drugs on platelet AMPA receptors would be critical in evaluating the putative effects of such drugs on CVD.
Palliation of Bone Cancer Pain by Antagonists of Platelet-Activating Factor Receptors  [PDF]
Katsuya Morita, Seiji Shiraishi, Naoyo Motoyama, Tomoya Kitayama, Takashi Kanematsu, Yasuhito Uezono, Toshihiro Dohi
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091746
Abstract: Bone cancer pain is the most severe among cancer pain and is often resistant to current analgesics. Thus, the development of novel analgesics effective at treating bone cancer pain are desired. Platelet-activating factor (PAF) receptor antagonists were recently demonstrated to have effective pain relieving effects on neuropathic pain in several animal models. The present study examined the pain relieving effect of PAF receptor antagonists on bone cancer pain using the femur bone cancer (FBC) model in mice. Animals were injected with osteolytic NCTC2472 cells into the tibia, and subsequently the effects of PAF receptor antagonists on pain behaviors were evaluated. Chemical structurally different type of antagonists, TCV-309, BN 50739 and WEB 2086 ameliorated the allodynia and improved pain behaviors such as guarding behavior and limb-use abnormalities in FBC model mice. The pain relieving effects of these antagonists were achieved with low doses and were long lasting. Blockade of spinal PAF receptors by intrathecal injection of TCV-309 and WEB 2086 or knockdown of the expression of spinal PAF receptor protein by intrathecal transfer of PAF receptor siRNA also produced a pain relieving effect. The amount of an inducible PAF synthesis enzyme, lysophosphatidylcholine acyltransferase 2 (LPCAT2) protein significantly increased in the spinal cord after transplantation of NCTC 2472 tumor cells into mouse tibia. The combination of morphine with PAF receptor antagonists develops marked enhancement of the analgesic effect against bone cancer pain without affecting morphine-induced constipation. Repeated administration of TCV-309 suppressed the appearance of pain behaviors and prolonged survival of FBC mice. The present results suggest that PAF receptor antagonists in combination with, or without, opioids may represent a new strategy for the treatment of persistent bone cancer pain and improve the quality of life of patients.
The Small GTPase Rap1b: A Bidirectional Regulator of Platelet Adhesion Receptors  [PDF]
Gianni Francesco Guidetti,Mauro Torti
Journal of Signal Transduction , 2012, DOI: 10.1155/2012/412089
Abstract: Integrins and other families of cell adhesion receptors are responsible for platelet adhesion and aggregation, which are essential steps for physiological haemostasis, as well as for the development of thrombosis. The modulation of platelet adhesive properties is the result of a complex pattern of inside-out and outside-in signaling pathways, in which the members of the Rap family of small GTPases are bidirectionally involved. This paper focuses on the regulation of the main Rap GTPase expressed in circulating platelets, Rap1b, downstream of adhesion receptors, and summarizes the most recent achievements in the investigation of the function of this protein as regulator of platelet adhesion and thrombus formation. 1. Introduction The adhesion of circulating blood platelets to the subendothelial matrix exposed upon vessel wall injury represents the initial event of the haemostatic process required to limit hemorrhage. Platelets express several membrane receptors specific for all the major adhesive ligands of the vascular extracellular matrix [1]. Among these, collagen is probably the most important subendothelial matrix component involved in thrombus formation, and platelet adhesion to collagen is associated with a complex pattern of activatory signaling pathways. Integrin α2β1 and glycoprotein VI (GPVI) are the two main platelet receptors for collagen and, in the rheological conditions of low shear rates, typically present in large veins and venules, are sufficient to mediate firm platelet adhesion. At high shear rates, characteristic of small arteries and stenotic vessels, platelets are unable to efficiently interact to exposed collagen fibers, and in these conditions adhesion is preceded by platelet tethering and rolling on the site of injury. This process is mediated by the membrane GPIb-IX-V complex, a platelet-specific receptor for the multimeric glycoprotein von Willebrand factor (VWF). At high shear stress, circulating VWF rapidly interacts with exposed collagen fibers and undergoes a conformational change that allows the interaction with the GPIb-XI-V complex, decelerating platelets and favoring the subsequent stable adhesion mediated by other platelet receptors [2]. The interaction of platelet adhesion receptors with subendothelial matrix components stimulates an intricate pattern of signal transduction pathways, that trigger spreading, secretion of soluble proaggregating molecules, thromboxane A2 (TxA2) synthesis and release, and phosphatydilserine exposure. These events recruit and activate additional circulating platelets to initiate a
The Toxicity of a Chemically Synthesized Peptide Derived from Non-Integrin Platelet Collagen Receptors
Thomas M. Chiang and V. Woo-Rasberry
Drug Target Insights , 2012,
Abstract: A chemically synthesized peptide derived from platelet non-integrin collagen receptor has been shown to be an effective agent for inhibiting collagen-induced platelet aggregation and adhesion of washed radiolabeled platelets onto natural matrices and collagen coated microtiter plates. In order to be a therapeutic agent, we have used a cell culturing system and an animal model to test its cytotoxicities. In cell culture experiments, the peptide is not toxic to MEG-01, a megakaryoblastic cell line. Prior to performing experiments in rats, the existence of both platelet type I and type III collagen receptors and its functional roles in rat platelets had to be established. In this investigation, we report that rat platelets contain both receptors and the cHyB peptide inhibits both type I and type III collagen-induced rat platelet aggregation. In addition, analysis of the rat sera collected at various time intervals following an injection of cHyB into the rat-tail vein, did not show an increase in the activity of key enzymes which indicate tissue and/or organ damage. These results suggest that the cHyB peptide is safe and its development into a potential therapeutic agent for inhibiting thrombi formation is possible.
The Toxicity of a Chemically Synthesized Peptide Derived from Non-Integrin Platelet Collagen Receptors
Thomas M. Chiang,V. Woo-Rasberry
Drug Target Insights , 2008,
Abstract: A chemically synthesized peptide derived from platelet non-integrin collagen receptor has been shown to be an effective agent for inhibiting collagen-induced platelet aggregation and adhesion of washed radiolabeled platelets onto natural matrices and collagen coated microtiter plates. In order to be a therapeutic agent, we have used a cell culturing system and an animal model to test its cytotoxicities. In cell culture experiments, the peptide is not toxic to MEG-01, a megakaryoblastic cell line. Prior to performing experiments in rats, the existence of both platelet type I and type III collagen receptors and its functional roles in rat platelets had to be established. In this investigation, we report that rat platelets contain both receptors and the cHyB peptide inhibits both type I and type III collagen-induced rat platelet aggregation. In addition, analysis of the rat sera collected at various time intervals following an injection of cHyB into the rat-tail vein, did not show an increase in the activity of key enzymes which indicate tissue and/or organ damage. These results suggest that the cHyB peptide is safe and its development into a potential therapeutic agent for inhibiting thrombi formation is possible.
The Toxicity of a Chemically Synthesized Peptide Derived from Non-Integrin Platelet Collagen Receptors
Thomas M. Chiang,V. Woo-Rasberry
Drug Target Insights , 2008,
Abstract: A chemically synthesized peptide derived from platelet non-integrin collagen receptor has been shown to be an effective agent for inhibiting collagen-induced platelet aggregation and adhesion of washed radiolabeled platelets onto natural matrices and collagen coated microtiter plates. In order to be a therapeutic agent, we have used a cell culturing system and an animal model to test its cytotoxicities. In cell culture experiments, the peptide is not toxic to MEG-01, a megakaryoblastic cell line. Prior to performing experiments in rats, the existence of both platelet type I and type III collagen receptors and its functional roles in rat platelets had to be established. In this investigation, we report that rat platelets contain both receptors and the cHyB peptide inhibits both type I and type III collagen-induced rat platelet aggregation. In addition, analysis of the rat sera collected at various time intervals following an injection of cHyB into the rat-tail vein, did not show an increase in the activity of key enzymes which indicate tissue and/or organ damage. These results suggest that the cHyB peptide is safe and its development into a potential therapeutic agent for inhibiting thrombi formation is possible.
Residual platelet reactivity during therapy with inhibitors of cyclooxigenase or adenosine diphosphate receptors  [cached]
A.A. Lomonosova,N.A. Mazur,E.A. Zolozova,E.V. Sayutina
Rational Pharmacotherapy in Cardiology , 2012,
Abstract: Aim. To compare effects of acetylsalicylic acid (ASA) and two clopidogrel drugs on residual platelet aggregative reactivity (RPAR).Material and methods. Patients (n=40) with ischemic heart disease aged under 70 years were involved into the crossover study. Clinical examination included questionnaire survey, blood pressure (BP) measurement, ECG registration, 24-hour ECG and BP monitoring, determination of blood levels of total cholesterol, high density lipoproteins, triglycerides, transaminases, and creatinine, complete blood cell count, including platelets number and hemoglobin level. Besides evaluation of the platelet aggregation by optical aggregometry was performed initially, after one week ASA treatment and after every next 3 week clopidogrel treatment period.Results. RPAR during ASA monotherapy was 56.4±0.3%. There were no significant differences in effects of original and generic clopidogrel on RPAR. Сlopidogrel therapy reduced RPAR more significantly (42.2±0.2%) than ASA monotherapy did (p=0.0003). Authors proposed definition for high level of RPAR during therapy - it is platelet aggregation more than 46%. Data analysis taking into account this criterion showed that a number of patients with high RPAR was 70 and 30% among patients treated with enterosoluble ASA and clopidogrel, respectively.Conclusion. Study results show that a significant number of patients receiving antiplatelet monotherapy does not achieve the target level of RPAR(<46%). These results may be a rationale for combined therapy in patients of this type.
Stabilizing Role of Platelet P2Y12 Receptors in Shear-Dependent Thrombus Formation on Ruptured Plaques  [PDF]
Reyhan Nergiz-Unal,Judith M. E. M. Cosemans,Marion A. H. Feijge,Paola E. J. van der Meijden,Robert F. Storey,J. J. J. van Giezen,Mirjam G. A. oude Egbrink,Johan W. M. Heemskerk,Marijke J. E. Kuijpers
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010130
Abstract: In most models of experimental thrombosis, healthy blood vessels are damaged. This results in the formation of a platelet thrombus that is stabilized by ADP signaling via P2Y12 receptors. However, such models do not predict involvement of P2Y12 in the clinically relevant situation of thrombosis upon rupture of atherosclerotic plaques. We investigated the role of P2Y12 in thrombus formation on (collagen-containing) atherosclerotic plaques in vitro and in vivo, by using a novel mouse model of atherothrombosis.
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