Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography

Lupus anticoagulants (LAC) consist of anti phospholipid antibodies, detected via their anti coagulant properties in vitro. Strong LAC relate to thromboembolic events, a hallmark of the anti-phospholipid syndrome. We have analyzed whether detection of this syndrome would benefit from thrombin generation measurements. Therefore, calibrated automated thrombography was done in normal plasma (n=30) and LAC patient plasma (n=48 non-anticoagulated, n=12 on oral anti coagulants), diluted 1: 1 with a normal plasma pool. The anti-beta(2)-glycoprotein I monoclonal antibody 23H9, with known LAC properties, delayed the lag time and reduced the peak height during thrombin generation induction in normal plasma dose-dependently (0-150 mu g/ml). At variance, LAC patient 1: 1 plasma mixtures manifested variable lag time prolongations and/or peak height reductions. Coupling these two most informative thrombin generation parameters in a peak height/lag time ratio,and upon normalization versus the normal plasma pool, this ratio distributed normally and was reduced in the plasma mixtures, for 59/60 known LAC plasmas. The normalized peak height/lag time ratio correlated well with the normalized dilute prothrombin time,diluted Russell's viper venom time and silica clotting time, measured in 1: 1 plasma mixtures (correlation coefficients 0.59-0.72). The anticoagulant effects of activated protein C (0-7.5 nM) or 23H9 (0-150 mu g/ml), spiked in the 1: 1 LAC plasma mixtures were reduced for the majority of patients, compatible with functional competition between patient LAC and activated protein C and LAC and 23H9, respectively. Hence,the normalized thrombin gene ration-derived peak height/lag time ratio identifies LAC in plasma with high sensitivity in a single assay, irrespective of the patient's treatment with oral anticoagulants

Hemostasis and inflammation: two of a kind?

Hemostasis is a defense mechanism to stop bleeding. Activated by vessel wall injury, it consists of intertwined activation of platelets and the coagulation cascade, tightly controlled by natural anticoagulants and the fibrinolytic system

Effect of VPAC1 Blockade on Adipose Tissue Formation and Composition in Mouse Models of Nutritionally Induced Obesity

Background. The pituitary adenylate cyclase activating polypeptide (PACAP) may affect adipogenesis and adipose tissue formation through interaction with its G-protein-coupled receptor VPAC1. Methods. We have used a monoclonal antibody (MAb 23A11) blocking VPAC1 in mouse models of nutritionally induced obesity. Results. Administration of MAb 23A11 (25 mg/kg body weight i.p. twice weekly) to 5-week old male C57Bl/6 mice kept on a high-fat diet for 15 weeks had no significant effect on weight gain, nor on subcutaneous (SC) or gonadal (GON) adipose tissue mass, as compared to the control MAb 1C8. However, adipocyte hypertrophy was observed in SC adipose tissue of MAb 23A11 treated mice. In a second study, 24 weeks old obese mice were treated for 5 weeks with MAb 23A11, without effect on body weight or fat mass, as compared to treatment with MAb 1C8. In addition, MAb 23A11 had no significant effect on glucose tolerance or insulin resistance in lean or obese C57Bl/6 mice. Conclusion. Blocking VPAC1 does not significantly affect adipose tissue formation in mouse models of diet-induced obesity, although it may be associated with mild adipocyte hypertrophy

The platelet ATP and ADP receptors.

peer reviewedThis review focuses on recent findings on the physiology of these platelet ADP and ATP receptors, their distinct downstream intracellular signaling pathways as well as on the available agonists, antagonists and inhibitors that allow their pharmacological discrimination

ATP Augments von Willebrand Factor-dependent Shear-induced Platelet Aggregation through Ca2+-Calmodulin and Myosin Light Chain Kinase Activation

peer reviewedShear stress triggers von Willebrand factor (VWF) binding to platelet glycoprotein Ibalpha and subsequent integrin alpha(IIb)beta(3)-dependent platelet aggregation. Concomitantly, nucleotides are released from plateletdense granules, and ADP is known to contribute to shear-induced platelet aggregation (SIPA). This study shows that ATP also contributes to SIPA. The ATP-gated P2X(1) ion channel induces MLC-mediated cytoskeletal rearrangements that increases platelet degranulation during VWF-triggered platelet activation

Dietary enrichment of apolipoprotein E-deficient mice with extra virgin olive oil in combination with seal oil inhibits atherogenesis

<p>Abstract</p> <p>Background</p> <p>In this study we investigated the antiatherogenic effect of dietary enrichment of a combination of extra virgin olive oil (EVO) and seal oil on apolipoprotein E-deficient (apoE^-/-).</p> <p>Methods</p> <p>Six-week-old female and male apoE^-/-mice were for 12 weeks fed a lipid rich diet containing 19.5% fat and 1.25% cholesterol without any supplement, with 1% (wt/wt) mixture of extra virgin olive and seal oil (EVO/n-3), or 1% corn oil, respectively.</p> <p>Results</p> <p>Supplementation with the combination of EVO/n-3 significantly reduced atherosclerotic lesion formation in the aortic arch, thoracoabdominal, and total aorta of female apoE^-/-mice. The effect was less pronounced in male mice and significant reduction was only observed in the thoracoabdominal region of the aorta. There were no differences or changes in dietary intake or body weight gain. However, compared to the other groups, plasma levels of triglycerides were reduced in both female and male mice fed the EVO/n-3 mixture. Male mice on both treatments showed reduced plasma cholesterol compared to the control mice after 12 weeks on diet.</p> <p>Conclusion</p> <p>Dietary supplementation of a marine/olive oil combination inhibits atherosclerotic lesion formation in the female apoE^-/-mice by antithrombotic, antihypertriglyceridemic, and antioxidant effects.</p

Исследования функциональности и состояния защитных сооружений ГО г. Юрги

Immunogenetics and cellular immunology of bacterial infectious disease

Разработка и исследование асинхронного электропривода с наблюдателем состояния

Выпускная квалификационная работа 109 с., 35 рис., 18 табл., 47 источников, 5 прил. Объектом исследования является дискретная математическая модель наблюдателя состояния полного порядка асинхронного двигателя. Цель работы – Разработка и исследование асинхронного электропривода с наблюдателем состояния В процессе исследования проводилось имитационное моделирование разработанной дискретной математической модели асинхронного двигателя и разработанной дискретной математической модели наблюдателя состояния полного порядкаFinal qualifying work 109 p., 35 fig., 18 tab., 47 sources, 5 adj. The object of research is a discrete mathematical model of the observer status of full order of the induction motor. Objective - Development and research of the asynchronous electric drive with observer status The study was conducted simulations developed discrete mathematical model of the induction motor and the developed mathematical model of discrete observer of full order stat

Kinetic Analysis of Substrate Utilization by Native and TNAP-, NPP1-, or PHOSPHO1-Deficient Matrix Vesicles

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Here, we have studied phosphosubstrate catalysis by osteoblast-derived MVs at physiologic pH, analyzing the hydrolysis of ATP, ADP, and PPi by isolated wild-type (WT) as well as TNAP-, NPP1- and PHOSPHO1-deficient MVs. Comparison of the catalytic efficiencies identified ATP as the main substrate hydrolyzed by WT MVs. The lack of TNAP had the most pronounced effect on the hydrolysis of all physiologic substrates. The lack of PHOSPHO1 affected ATP hydrolysis via a secondary reduction in the levels of TNAP in PHOSPHO1-deficient MVs. The lack of NPP1 did not significantly affect the kinetic parameters of hydrolysis when compared with WT MVs for any of the substrates. We conclude that TNAP is the enzyme that hydrolyzes both ATP and PPi in the MV compartment. NPP1 does not have a major role in PPi generation from ATP at the level of MVs, in contrast to its accepted role on the surface of the osteoblasts and chondrocytes, but rather acts as a phosphatase in the absence of TNAP. © 2010 American Society for Bone and Mineral Research