bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Comparative Study of potential anxiolytic effect of Vitamin C and Buspirone in rats
Authors: Soliman Ghada Farouk , Khattab Aida Abdalla , Habil Mariam Refaat
Published: December 2019

Background: Anxiety disorders are the most common of all mental health problems. They are more prevalent among women than among men, and they affect children as well as adults. The aim of the current study is to evaluate this problem via an experimental animal model and try to explore its possible mechanisms by studying the effect of Vitamin C compared to Buspirone on anxiety in rats induced by Monosodium Glutamate (MSG).Materials and Methods: 56 healthy adult male albino rats (Sprague-Dawley) weighing 200-250 gm were used and divided into 7 groups (8 rats each). The first and the second groups were provided with normal saline and MSG at a dose of (2 mg/g p.o.) respectively. The other five groups were given MSG and treated daily in the following way: The third and fourth groups were treated with Vitamin C (100, 200 mg/kg p.o) respectively. The fifth group was treated with only Buspirone (10 mg/kg p.o.), while the last sixth and seventh groups were given a combination of Buspirone and Vitamin C with (100, 200 mg/kg) respectively. After 3 weeks, the open field and successive alleys tests were used to assess behavioral changes. The percentage change of systolic blood pressure (SBP) was measured. Additionally, glutathione reductase (GR), malondialdehyde (MDA), and corticosterone levels were determined biochemically.Results: The results after 3 weeks revealed that MSG group showed significant anxiogenic effects in both behavioral tests, with an increased percentage change of SBP in addition to increased malondialdehyde and corticosterone level measured statistically. While the results of the treated groups revealed that the Vitamin C (100mg/kg) treated group demonstrated significant improvement in anxiety levels in the open field test, there were no significant changes in the biochemical assessment. However, vitamin C (200mg/kg) treated group revealed a significant anxiolytic effect in behavioral tests, improved glutathione and malondialdehyde with low corticosterone level. Administration of buspirone revealed significant anxiolytic effects, which is lower than that of vitamin C (200mg/kg). But it caused significant increase in the oxidative stress and corticosterone levels. A combination of buspirone with Vitamin C (200mg/kg) only demonstrated significant anxiolytic effect in both tests and a significant decrease of corticosterone.Conclusion: MSG has neurotoxic effect leading to anxiogenic behaviors in rats which are opposed by Vitamin C. Furthermore, as an antioxidant, vitamin C protects against the oxidative stress induced by MSG. Moreover, it lowers the high corticosterone level associated with MSG or buspirone administration.Key Words: MSG, vitamin C, buspirone, glutathione reductase, malondialdehyde, open field, successive alleys
Analysis technology conversion of renewable energy sources in the engine fuel
Authors: Bodyakina T. V , Boloev P. A , Gergenova T. P
Published: December 2019

The increase in the share of renewable energy sources as motor fuel of automotive vehicles can significantly affect the environmental and energy safety in the operation of equipment. The aim of the study is to analyze the technologies of conversion of renewable energy sources for use as a motor fuel. The raw energy medium primarily includes hydrocarbon compounds, which process of thermochemical transformation is accompanied by the release of the main target component - hydrogen. The presence of the hydrogen component causes unique kinetic and environmental indicators of its combustion, high efficiency of the engine operating cycle. Esters are derivatives of organic or inorganic acids and alcohols, they are found mainly in essential oils and make up the bulk of vegetable and animal oils. Currently, dimethyl ether is considered as one of the most promising fuels for diesel engines. In this regard, the transfer of diesels on the air does not require special measures for the forced ignition of the combustible mixture. If the raw material origin and the cost of production of dimethyl ether are taken into account, this is the most promising motor fuel. A positive property of vegetable oils is the ability to mix in any proportions with gasoline, kerosene and diesel fuel, which allows to obtain biofuels with desired physical and chemical properties. The article deals with esters, methods of their production, vegetable oils. It describes the ways to achieve the necessary properties of alternative energy as motor fuel. The results of the comparative analysis of processing technologies of renewable energy in the fuel for automotive engines are given. It substantiates the potential use of alternative energy sources in the energy structure of the agricultural complex.
Methods of calculating the resistance and the moment of resistance to cutting the soil with a straight blade knife cutters
Authors: Konstantinov Y. U.V
Published: December 2019

During the process of cutting the soil, the blade knives of the cutter and its hub experience cyclic loads. Therefore, along with the calculation of the knives for static strength, their calculation for fatigue strength is necessary. To carry out such a calculation, it is necessary to know the dependence of the main vector of the soil resistance forces to cutting and the main moment of these forces on the angle of rotation of the cutter. The construction of the methodology for calculating the resistance and the moment of resistance to cutting the soil with a plate knife, depending on the angle of rotation of the cutter, is the purpose of this study. Based on the proposed mathematical model of the interaction of the knife blade with the soil, such a calculation method has been developed. The obtained analytical dependences also include the geometric and operational parameters of the cutter. The relative depth of the cutter and its kinematic parameter, which is equal to the ratio of the peripheral speed of the end of the knife to the speed of the translational movement of the cutter, are taken as regime dimensionless parameters. It was shown that the resultant reaction of the soil to the knife blade during cutting periodically changes its value, direction and application point, and the maximum values of the driving force, the modulus of the resultant forces of soil reactions and the modulus of the total moment of soil resistance to cutting monotonously increase with an increase in the relative depth of the cutter. The angle, which is the resultant of the forces of soil reactions with the direction of movement of the cutter, decreases almost linearly with an increase in the angle of rotation. The technique allows to significantly simplify experiments to determine the power characteristics of the cutter and significantly reduce their volume, since it requires the determination of only one empirical constant. Due to the generality of the basic starting points, the proposed methodology can be mainly transferred to other rotational working bodies. Laboratory experiments conducted in the soil channel confirmed the adequacy of the proposed mathematical model for the interaction of the cutter blade with the soil.
Methodology for multicriteria assessment and selection of an effective method of grain disinfection
Authors: Pahomov A. I
Published: December 2019

High-quality crop products should not contain extraneous and dangerous substances of both natural and artificial origin. Natural contaminants include parasitic micro-fungi and bacteria; artificial ones include chemical compounds in the form of pesticides and fertilizers. Pesticides, in one way or another solving the problem of disinfection, are themselves very dangerous. In addition, their constant use leads to mutations of parasitic microorganisms in the direction of extremely stable species, i.e. the problem of resistance. To avoid these shortcomings, there are alternative disinfection methods based on various types of electromagnetic energy. A variety of such methods raises the purpose of their objective assessment, including in comparison with chemical etching. This determined the purpose of the study, which consists in developing a scientifically based methodology for multicriteria assessment and choosing an effective method of grain disinfection. The object of the study was the chemical and electrophysical methods of disinfection, the subject of the study - the patterns of choosing the best of them. The novelty was made up of the stages of the methodology: structuring the attribute space, compiling a hierarchical diagram of groups of attributes, determining weighting factors and estimates based on the specifics of agricultural production. In mathematical tools, the maximum sum of weighted estimates method is used, according to which the integral criterion F is calculated. The technique is suitable for any disinfection methods with any number of signs and alternatives. An example of its application for four alternatives is given: chemical etching, microwave disinfection, SHV disinfection, disinfection with a low-frequency magnetic field (LMF). At the same time, the advantage of the LMF method was established, which received the maximum integral estimate F = Fmax = 0,864. The conclusions are drawn about the reliability of the methodology, the possibility of its application in an expanded space of signs, which gives an updated assessment.
Vascular smooth muscle cells exhibit a progressive loss of rigidity with serial culture passaging
Authors: Dinardo Carla Luana , Venturini Gabriela , Omae Samantha Vieira , Zhou Enhua H. , da Motta-Leal-Filho Joaquim Maurício , Dariolli Rafael , Krieger José Eduardo , Alencar Adriano Mesquita , Costa Pereira Alexandre
Published: December 2019

One drawback of in vitro cell culturing is the dedifferentiation process that cells experience. Smooth muscle cells (SMC) also change molecularly and morphologically with long term culture. The main objective of this study was to evaluate if culture passages interfere in vascular SMC mechanical behavior. SMC were obtained from five different porcine arterial beds. Optical magnetic twisting cytometry (OMTC) was used to characterize mechanically vascular SMC from different cultures in distinct passages and confocal microscopy/western blotting, to evaluate cytoskeleton and extracellular matrix proteins. We found that vascular SMC rigidity or viscoelastic complex modulus (G) decreases with progression of passages. A statistically significant negative correlation between G and passage was found in four of our five cultures studied. Phalloidin-stained SMC from higher passages exhibited lower mean signal intensity per cell (confocal microscopy) and quantitative western blotting analysis showed a decrease in collagen I content throughout passages. We concluded that vascular SMC progressively lose their stiffness with serial culture passaging. Thus, limiting the number of passages is essential for any experiment measuring viscoelastic properties of SMC in culture.
Swirling flow can suppress monocyte adhesion in the flow disturbance zones of the endovascular stent
Authors: Chen Zengsheng , Zhang Xiwen , Deng Xiaoyan
Published: December 2019

Adhesion of monocytes (U-937 cells) along a silicone tube deployed with circular ring stents was studied to test the hypothesis that by intentionally inducing swirling flow in an endovascular stent, the adhesion of monocytes would be suppressed. The results revealed that under a normal flow condition, the flow disturbance created by the circular ring stents enhanced the adhesion of U-937 cells in the silicone tube. By inducing a swirling flow in the silicone tube, the average wall shear stress (WSS) in the tube with the circular ring stents was elevated and significantly suppressed the adhesion density of U-937 cells to the surface in the disturbed flow zones to a level equal to that when no stents were deployed in the tube. The results also showed that, due to the attenuation of the swirling flow along the tube, the adhesion density of U-937 cells increased monotonically along the tube, indicating that the adhesion density was negatively correlated with the strength of the swirling flow. Thus, the present study suggests that intentionally introducing swirling flow in an artery deployed with stents may be a solution to solve the problem of stent restenosis by restraining the adhesion of monocytes.
Contactless cell trapping by the use of a uniform AC electric field
Authors: Tada Shigeru , Natsuya Tomoyuki , Tsukamoto Akira , Santo Yudai
Published: December 2019

The AC electric field-driven manipulation of suspended polarizable particles has become a major technique in micro- and nano-devices. In the present study, suspensions of cultured HeLa cells in isotonic solution were used to explore the mechanisms underlying the suspension behaviors during exposure to a uniform AC electric field of strength Erms=1.67×104 V/m at frequency 1 kHz. Molecular dynamics (MD) simulations based on the Langevin equation of particle kinetics were performed to elucidate the corresponding problem. A theoretical model to compute the trajectories of individual cells under the action of electro-mechanical, viscous and gravitational forces in the suspending medium was newly developed. Numerical computations demonstrated that the suspended cells began to aggregate to form chainlike clusters along the direction of the uniform AC electric field at an earlier stage of the field application. Moreover, the predicted results were similar to the experimental results. These findings indicate that the chain-like cell clustering arises from the long-range dipole–dipole interaction of neighboring cells, but under the action of the gravitational force that likely hinders the growth of clusters in the vertical direction.
Medium with blood-analog mechanical properties for cardiovascular tissue culturing
Authors: van den Broek Chantal N. , Pullens Rolf A.A. , Frøbert Ole , Rutten Marcel C.M. , den Hartog Wilfred F. , van de Vosse Frans N.
Published: December 2019

Physiological wall shear rates and stresses in vessel culture or tissue engineering are relevant for maintaining endothelial cell (EC) integrity. To this end, the culture medium should have an appropriate viscosity. The viscosity of a standard culture medium was increased using xanthan gum (XG) and compared with literature data on whole blood, resulting in a medium with blood-analog shear-thinning behavior (XG-medium). The measured osmolality of the XG-medium was 285±2 mOsm kg−1, which is within a physiologically acceptable range. The XG-medium was compared to standard medium to verify whether XG alters vascular cell function. First, the effect of XG on the growth of human EC monolayers was determined. In addition, to study whether XG changes drug-induced vasoconstriction or endothelium-dependent vasodilation, different drugs were administered to porcine coronary artery rings in a solution with or without XG, measuring the isometric force developed. XG did not influence EC growth, nor did it change drug-induced vascular tone. Moreover, the ECs aligned in the direction of flow after 24 h of physiological shearing with XG-medium. We conclude that, unlike standard culture media, XG-medium as a blood-analog culture medium has rheological properties suitable for use in vessel culture and tissue engineering to induce physiological wall shear stresses at physiological flow rates.
In vivo correlates of altered blood rheology
Authors: Baskurt Oguz K.
Published: December 2019

It is has been known for more than 80 years that compared to in vitro determinations, blood behaves as a less viscous fluid under in vivo flow conditions. The experiments of Whittaker and Winton were among the first dealing with the in vivo effects of altered blood rheology, and experimental studies during the second half of 20th century have provided additional evidence for the complexity of in vivo hemodynamics–hemorheology relationships. Careful studies indicate that the impact of a given blood rheology alteration is determined by the properties of the experimental model (e.g., organ or tissue under investigation), experimental approach (e.g., intravital microscopy, whole organ perfusion) and method used to modify blood rheology. In addition, vascular control mechanisms may play a major role in the resulting hemodynamic effects of a hemorheological alteration: (1) a response simply related to metabolic autoregulation in which there is a compensatory vasodilation due to altered in vivo blood flow and organ/tissue hypoxia; (2) modulation of endothelial function (e.g., NO production) via altering wall shear stress, thereby leading to changes of vascular hindrance. The in vivo effects of altered red blood cell (RBC) aggregation have been investigated in various experimental models. A novel technique for modifying RBC aggregability (i.e., intrinsic tendency of RBC to aggregate) by covalent attachment of specific co-polymers has been used in some studies, and has provided data reflecting the specific effects of RBC aggregation without the influence of altered suspending phase properties. These data indicate that both the magnitude of the hemodynamic effect and the direction of the alteration depend on the intensity of RBC aggregation. Using the same novel technique, RBC aggregation has been shown to be an important determinant of endothelial function through its effects on RBC axial distribution and wall shear stress. These somewhat diverse findings can be explained by considering the contribution of various in vivo hemorheological mechanisms that have opposite effects on in vivo flow resistance.
Traumatic loading of articular cartilage: Mechanical and biological responses and post-injury treatment
Authors: Natoli Roman M. , Athanasiou Kyriacos A.
Published: December 2019

This review discusses a framework for studying injurious loading of articular cartilage, which can lead to post-traumatic osteoarthritis. The framework separates the mechanical from the biological response of the tissue to injury. The mechanical response is governed by the tissue's biomechanical behavior and sets off mechano-transductive pathways. These pathways then determine the biological response. The mechanical response of cartilage to injury has been studied by analytical and computational models of injurious loading, joint contact, and surface fissuring. These models have identified shear and tensile stresses as important parameters governing articular cartilage failure in response to mechanical injury. Further, measurement of cartilage's material properties during impact loading has shown that the tissue is significantly stiffer than predicted from quasi-static testing. In terms of the biological response, cell death and sulfated glycosaminoglycan (sGAG) loss from the tissue are early degradative changes that lead to decreased tissue function. These biological sequelae have also been the subject of targeted intervention strategies post-injury. Some success has been found for decreasing cell death and sGAG loss using various bioactive agents. The framework and treatments reviewed here may be useful starting points in the study of mechanical injury to other tissues.
An energy-rate based blood viscosity model incorporating aggregate network dynamics
Authors: Kaliviotis Efstathios , Yianneskis Michael
Published: December 2019

Existing time-dependent blood viscosity models that involve aggregation dynamics are mainly based on structural variables and/or viscoelastic models in order to describe the bulk mechanical properties of the fluid, but the implications of important characteristics of blood microstructure, such as the time- and flow-dependent characteristics of the red blood cell network developed due to aggregation at low shear rates, have not been thoroughly investigated. In this paper a time-dependent blood viscosity model is developed based on an energy-rate model previously proposed (Skalak et al., Biophys. J. 35 (1977), 771–781), which describes the total work needed to overcome the various forces developed between aggregated cells, including the adhesive, elastic and dissipative forces. Novel formulations of the forces acting on the fluid are developed and implemented in a volume-averaged version of the energy-rate model. The calculation of the viscosity is based on the relationship between the rate of energy changes and shear stress per unit volume of the fluid. The results show that network characteristics may significantly influence the viscosity blood at low shear rates and exhibit good agreement with experimental observations.
Long term shear stress leads to increased phosphorylation of multiple MAPK species in cultured human aortic endothelial cells
Authors: Shepherd Robert D. , Kos Stephanie M. , Rinker Kristina D.
Published: December 2019

Fluid dynamics strongly influences endothelial cell function, and participates in the localization of atherosclerotic plaques at blood vessel branches. We investigated the hypothesis that wild-type human aortic endothelial cells (HAEC) exposed to prolonged pulsatile flow stimulation have levels of phosphorylated mitogen-activated protein kinases (MAPK) that are significantly greater than those observed in statically grown cultures. HAEC were exposed to pulsatile laminar shear stress in a parallel-plate flow chamber and analyzed for levels of phosphorylated ERK, JNK and p38 at 1, 10 and 20 h. While some MAPK exhibited alternating patterns of phosphorylation, others were characterized by steady increases or unchanged profiles until the terminal (20 h) time point. However, at 20 h, each MAPK demonstrated an increase in phosphorylation versus statically cultivated cells. Further, 20 h cultures from 10 dyn/cm2 pulsatile shear stress had higher levels of phosphorylation for each MAPK than those from 2 dyn/cm2. The finding that MAPK species can be phosphorylated in response to a prolonged pulsatile shear stress in both a time and magnitude dependent manner is an interesting result that may help to explain how the differential behaviors observed between cells from different flow environments can be generated and maintained.
Biomechanical, morphological and zero-stress state characterization of jugular vein remodeling in arteriovenous fistulas for hemodialysis
Authors: Kritharis Eleftherios P. , Kakisis John D. , Giagini Athina T. , Manos Themistoklis , Stergiopulos Nikos , Tsangaris Sokrates , Sokolis Dimitrios P.
Published: December 2019

While the role of hemodynamic variables on the development of intimal hyperplasia in arteriovenous fistulas for hemodialysis has been examined, less is known about the intramural biomechanical factors. In this study, arteriovenous fistulas were created by implantation of e-PTFE grafts between carotid artery and jugular vein in healthy pigs. In vivo recordings exhibited a three-fold pressure and flow elevation in grafted veins after fistula creation, remaining so until sacrifice. The chief morphological observation in grafted vessels was wall thickening at two weeks, serving to restore intramural stresses to homeostatic levels, and a less marked internal diameter enlargement, gradually normalizing intimal shear after four weeks. The residual strains and opening angle, specifying the zero-stress configuration, increased with differences reaching significance at twelve weeks. Association with histomorphological findings on intima, media and adventitia growth disclosed a correlation between intimal hyperplasia and opening angle increase. Elastin and cellular contents diminished opposite to collagen content, most differences occurring within the first four weeks after grafting. Inflation/extension testing showed that post-fistula the vein wall became progressively thicker and stiffer, lacking restoration of compliance to baseline levels. The present data may further our understanding of the dynamics of venous biomechanical remodeling under pressure and flow-overload conditions.
A new viscosupplement based on partially hydrophobic hyaluronic acid: A comparative study
Authors: Finelli Ivana , Chiessi Ester , Galesso Devis , Renier Davide , Paradossi Gaio
Published: December 2019

A novel partially hydrophobized derivative of hyaluronic acid (HYADD®4), containing a low number of C16 side-chains per polysaccharide backbone, provides injectable hydrogels stabilized by side-chain hydrophobic interactions. The rheological properties of Hymovis®, a physical hydrogel based on the hyaluronic acid derivative HYADD®4, were evaluated using as reference a solution of the parent natural polysaccharide, hyaluronic acid. The rheological measurements were performed both in flow and oscillation regimes at the physiological frequency values of the knee, typically spanning the range from 0.5 Hz (walking frequency) to 3 Hz (running frequency). Moreover, the viscoelastic features of Hymovis® were compared with the market-available viscosupplementation products in view of its use in joint diseases.

The different behavior of the investigated materials in crossover frequency measurements and in structure recovery experiments can be explained on the basis of the structural and dynamic properties of the polymeric systems.
Apelin-induced hemorheological alterations in DOCA-salt hypertensive rats
Authors: Kursunluoglu-Akcilar Raziye , Kilic-Toprak Emine , Kilic-Erkek Ozgen , Turgut Sebahat , Bor-Kucukatay Melek
Published: December 2019

Apelin is a hypotensive peptide. Red blood cell (RBC) deformability and aggregation were previously demonstrated to be altered in various hypertension (HT) models. In the present study, we investigated possible alterations in RBC deformability and aggregation in response to apelin in DOCA-salt hypertensive rats. Rats were randomly divided into 4 groups: Control (C), Hypertension (HT), Apelin, and Apelin + Hypertension (Apelin + HT). HT was induced by injection of DOCA-salt (25 mg/kg, s.c.) twice weekly for 4 weeks, whereas apelin was administered (200 μg/kg i.p.) for 17 days. RBC deformability and aggregation were determined using an ektacytometer. Blood pressure was monitored using a tail cuff system. Systolic blood pressure was decreased in the Apelin and Apelin + HT groups and increased in the HT group. RBC deformability was not significantly altered in the HT group. Apelin administration induced a statistically significant increase in RBC deformability in control animals, whereas erythrocytic deformability in the Apelin + HT group was decreased compared to the Apelin group. RBC aggregation of hypertensive animals was reduced compared to controls. Apelin administration induced increased RBC aggregation in hypertensive rats. Our results showed favorable effects of apelin on RBC deformability in control animals, but not in hypertensive rats.
Red blood cell deformability is very slightly decreased in erythropoietin deficient mice
Authors: Pichon Aurélien , Lamarre Yann , Voituron Nicolas , Marchant Dominique , Vilar José , Richalet Jean-Paul , Connes Philippe
Published: December 2019

The present study compared the hemorheological properties between Epo-TAgh mice (a model of erythropoietin deficient mice) and wild-type (WT) control mice. Blood viscosity was determined at several shear rates using a cone-plate viscometer at native and adjusted hematocrit (i.e. 40%). Red blood cell (RBC) deformability was measured by ecktacytometry at several shear stresses and RBC aggregation properties by backscattered technique at adjusted hematocrit (i.e. 40%). Epo-TAgh mice had severe anemia (very low hematocrit), decreased blood viscosity at native hematocrit and slightly reduced RBC deformability at high shear stresses in comparison with WT mice. Blood viscosity at adjusted hematocrit (i.e. 40%) was not different between WT and Epo-TAgh mice. RBC aggregation did not differ between the two mice models. These findings suggest a role of erythropoietin in the regulation of RBC deformability.
Fibrinogen modulates leukocyte recruitment in vivo during the acute inflammatory response
Authors: Vitorino de Almeida V. , Silva-Herdade A. , Calado A. , Rosário H.S. , Saldanha C.
Published: December 2019

Besides playing an important role in blood hemostases, fibrinogen also regulates leukocyte function in inflammation. Our previous in vitro studies showed that the adhesive behaviour of the neutrophil is modulated by soluble fibrinogen when present at a physiological concentration. This led us to propose that this plasma glycoprotein might further influence leukocyte recruitment in vivo and thus contribute to the inflammatory response. To address this in vivo, leukocyte recruitment was here investigated under acute inflammatory conditions in the absence of soluble fibrinogen in the blood circulation. For such, intravital microscopy on mesentery post-capillary venules was performed on homozygous fibrinogen α chain-deficient mice ((α−/−) mice). Acute inflammatory states were induced by perfusing platelet activating factor (PAF) over the exposed tissue. As control animals, two groups of mice expressing soluble fibrinogen in circulation were used, namely, C57BL/6 wild type animals and heterozygous fibrinogen α chain-deficient mice ((α+/−) mice). Under acute inflammatory conditions, an abnormal pattern of recruitment was observed for leukocytes in homozygous (α−/−) mice in comparison to both control groups. In fact, the former exhibited a significantly decreased number of rolling leukocytes that nevertheless, migrated with increased rolling velocities when compared to leukocytes from control animals. Consistently, homozygous mice further displayed a diminished number of adherent leukocytes than the other groups. Altogether our observations led us to conclude that leukocyte recruitment in homozygous (α−/−) mice is compromised what strongly suggests a role for soluble fibrinogen in leukocyte recruitment in inflammation.
An in vitro study on the modulation of the neutrophil adhesive behavior by soluble fibrinogen
Authors: de Almeida V. Vitorino , Calado A. , Silva-Herdade A.S. , Rosário H.S. , Saldanha C.
Published: December 2019

Fibrinogen constitutes an important plasma glycoprotein involved in hemostasis and in inflammation. Previously, we have shown that at physiological concentrations, soluble fibrinogen is able to modulate the pattern of neutrophil activation. This led us to propose that under these conditions, fibrinogen could as well interfere with the adhesive behaviour of circulating neutrophils which is of utmost importance in their recruitment to the vascular wall during inflammatory processes. To address our working hypothesis, in vitro adhesion assays were here performed in a flow chamber by using primary cultures of human umbilical vein endothelial cells (HUVEC) and neutrophils isolated from peripheral venous blood of healthy human donors. In the presence of a physiological concentration of soluble fibrinogen (300 mg/dL), we observed that despite the number of neutrophils rolling on an activated endothelium was not affected, their rolling velocity was increased in comparison to that of non-activated neutrophils. Consequently as expected, the number of fibrinogen-treated neutrophils adhering to activated HUVEC monolayers was significantly diminished. Overall, we have here demonstrated that at least in vitro, soluble fibrinogen under physiological concentrations is able to modulate the interaction of neutrophils with the vascular endothelium. In vivo studies will enable us in the future to study the physiological relevance of these findings and further to understand the mechanisms underlying this function.
Deep vein thrombus formation induced by flow reduction in mice is determined by venous side branches
Authors: Brandt Moritz , Schönfelder Tanja , Schwenk Melanie , Becker Christian , Jäckel Sven , Reinhardt Christoph , Stark Konstantin , Massberg Steffen , Münzel Thomas , von Brühl Marie-Luise , Wenzel Philip
Published: December 2019

BACKGROUND: Interaction between vascular wall abnormalities, inflammatory leukocytes, platelets, coagulation factors and hemorheology in the pathogenesis of deep vein thrombosis (DVT) is incompletely understood, requiring well defined animal models of human disease. METHODS AND RESULTS: We subjected male C57BL/6 mice to ligation of the inferior vena cava (IVC) as a flow reduction model to induce DVT. Thrombus size and weight were analyzed macroscopically and sonographically by B-mode, pulse wave (pw) Doppler and power Doppler imaging (PDI) using high frequency ultrasound. Thrombus size varied substantially between individual procedures and mice, irrespective of the flow reduction achieved by the ligature. Interestingly, PDI accurately predicted thrombus size in a very robust fashion (r2 = 0.9734, p < 0.0001). Distance of the insertion of side branches from the ligature significantly determines thrombus weight (r2 = 0.5597, p < 0.0001) and length (r2 = 0.5441, p < 0.0001) in the IVC, regardless of the flow measured by pw-Doppler with distances <1.5 mm drastically impairing thrombus formation. Occlusion of side branches prior to ligation of IVC did not increase thrombus size, probably due to patent side branches inaccessible to surgery. CONCLUSION: Venous side branches influence thrombus size in experimental DVT and might therefore prevent thrombus formation. This renders vessel anatomy and hemorheology important determinants in mouse models of DVT, which should be controlled for.
Homocysteine levels in patients with primary and secondary Raynaud's phenomenon. Its association with microangiopathy severity
Authors: Vayá Amparo , Sánchez Fernando , Todolí Jose , Calvo Javier , Alis Rafael , Collado Susana , Ricart Jose M.
Published: December 2019

The association between hyperhomocysteinemia (HHcy) and Raynaud's phenomenon (RP) remains a matter of debate. In 18 primary RP, 23 secondary RP and 41 controls, we investigated homocysteine (Hcy) levels along with biochemical and inflammatory parameters. The Hcy levels in both primary and secondary RP were elevated when compared with controls (p < 0.05 and p < 0.01, respectively). As age was higher in secondary RP as compared with controls (p < 0.01), both primary and secondary RP were age-matched with a corresponding control group, and with Hcy maintaining its statistical significance (p < 0.05). No differences in creatinine, B12 vitamin or folic acid were observed between groups (p > 0.05), or in the prevalence of cardiovascular risk factors (p > 0.05). When patients were classified according to presence or absence of digital ulcers, as a sign of microangiopathy severity, the former showed higher Hcy levels than the latter (p = 0.035). Our results indicate that both primary and secondary RP patients show a mild increase in Hcy levels, which is not related to age, vitamin deficiencies or impaired renal function, but is related to microangiopathy severity. Therefore the association of HHcy and RP suggest that Hcy may contribute to endothelial dysregulation, which characterizes this disease. Specific studies should be designed to elucidate the pathogenesis of HHcy in these patients.
Studies on metabolically depleted erythrocytes
Authors: Reinhart S.A. , Schulzki T. , Bonetti P.O. , Reinhart W.H.
Published: December 2019

Erythrocytes kept outside the blood circulation undergo progressive changes in metabolism, shape and function, which was the topic of this study. For that purpose, blood anticoagulated with either heparin, citrate or EDTA was incubated at temperatures of 5°C, 22°C or 37°C for 0 h, 24 h and 48 h, respectively. A temperature- and time-dependent decrease of glucose and ATP and increase of lactate and LDH were observed. An erythrocyte swelling and echinocytic shape transformation, which was also time- and temperature-dependent, was seen. Density-separated young and old erythrocytes behaved similarly. The degree of echinocytic shape transformation correlated with the increase in blood viscosity at high shear rate. Echinocytosis was partially reversible when erythrocytes were suspended in buffer containing 0.2% albumin. This phenomenon is specific for albumin, since molecules with a similar molecular weight (dextran 70, heat shock protein, protein C) had no effect. These finding may have an impact on blood banking and transfusion medicine.
Influence of blood lipids on plasma and blood viscosity
Authors: Irace Concetta , Carallo Claudio , Scavelli Faustina , Esposito Teresa , De Franceschi Maria Serena , Tripolino Cesare , Gnasso Agostino
Published: December 2019

BACKGROUND AND AIM: The relationship between hyperlipidemia and blood and plasma viscosity is not completely clear. While increasing viscosity is often reported with increasing blood lipids, lipid-lowering treatments are often unable to normalize the viscosity values. Aim of this study is to try to clarify the relationship between blood lipids and viscosity. METHODS AND RESULTS: Apparently healthy subjects were enrolled (n = 410). Smokers, diabetics, obese, and hypertriglyceridemic (above 400 mg/dl) were excluded. Blood (at shear rate 225/s) and plasma viscosity were measured at 37°C. Erythrocyte rigidity (Tk) was calculated according to Dintenfass. Blood lipids and glucose were measured by routine methods. Hyperlipidemic subjects (n = 315) had higher values of plasma viscosity (1.44 ± 0.13 vs. 1.40 ± 0.12 cP, p = 0.007), and blood viscosity (4.51 ± 0.54 vs. 4.35 ± 0.55 cP, p = 0.013), compared to normolipidemic subjects (n = 95). In simple correlation analysis, plasma viscosity was directly associated with LDL cholesterol, and inversely with Tk and HDL cholesterol. In multiple regression analysis the association with LDL and HDL was strengthened, though these two variables as a whole accounted for only 5% (adjusted R2) of the variability of plasma viscosity. Blood viscosity was significantly associated with haematocrit, plasma viscosity, Tk and all considered variables but age in simple correlation analysis, but only with haematocrit, plasma viscosity and Tk in multiple regression analysis. CONCLUSIONS: LDL cholesterol and HDL cholesterol influence plasma viscosity, but not blood viscosity. Triglycerides up to values of 400 mg/dl do not seem to have important effects, at least in apparently healthy subjects and at the shear rates used in the present study. The contribution of LDL and HDL cholesterol to plasma viscosity seems however quite limited.
Strict heart rate control attenuates prothrombotic state and platelet activity in patients with non-valvular permanent atrial fibrillation
Authors: Erdogan Dogan , Uysal Bayram Ali , Aksoy Fatih , Kaya Selcuk , Icli Atilla , Ceyhan Betul Mermi , Ozaydin Mehmet
Published: December 2019

BACKGROUND: The underlying mechanisms of increased risk of thrombo-embolism in atrial fibrillation (AF) are not completely understood; however, substantial evidence supports that AF is associated with a prothrombotic state. Accordingly, we hypothesized that strict rate control could attenuate platelet activity and thrombotic state in patients with non-valvular AF. METHODS: Seventy-five patients with non-valvular AF were divided into 2 groups based on heart rate: (1) normal ventricular rate (n = 34, 18 female) and (2) high ventricular rate (n = 39). Thirty-three sex- and age-matched subjects in sinus rhythm were included as control. Thirty patients with high ventricular rate (16 female) were successfully followed. Markers of platelet function were measured at baseline and repeated 1-month after adequate rate control in high ventricular rate group. RESULTS: Serum fibrinogen levels were significantly higher in AF patients with high ventricular rate than that in controls. Mean platelet volume, soluble CD40L and β-Thromboglobulin were significantly higher in AF patients with high ventricular rate than those in both AF patients with normal ventricular rate and controls. Soluble CD40L and β-Thromboglobulin were significantly higher in AF patients with normal ventricular rate than those in controls. One-month after adequate rate control, serum fibrinogen, soluble CD40L and β-Thromboglobulin levels significantly decreased (from 2.26 ± 1.02, 85.01 ± 37.05, 3.10 ± 0.90 to 1.55 ± 1.08, 66.34 ± 33.72, 2.71 ± 0.53; p < 0.001, p = 0.002, p = 0.03, respectively) in high ventricular rate group. CONCLUSIONS: AF patients with high ventricular rate had increased indices of platelet activity and thrombotic state. Furthermore, strict rate control significantly decreased indices of thrombotic state and platelet activity in those patients.
The relationship between red blood cell deformability metrics and perfusion of an artificial microvascular network
Authors: Sosa Jose M. , Nielsen Nathan D. , Vignes Seth M. , Chen Tanya G. , Shevkoplyas Sergey S.
Published: December 2019

The ability of red blood cells (RBC) to undergo a wide range of deformations while traversing the microvasculature is crucial for adequate perfusion. Interpretation of RBC deformability measurements performed in vitro in the context of microvascular perfusion has been notoriously difficult. This study compares the measurements of RBC deformability performed using micropore filtration and ektacytometry with the RBC ability to perfuse an artificial microvascular network (AMVN). Human RBCs were collected from healthy consenting volunteers, leukoreduced, washed and exposed to graded concentrations (0–0.08%) of glutaraldehyde (a non-specific protein cross-linker) and diamide (a spectrin-specific protein cross-linker) to impair the deformability of RBCs. Samples comprising cells with two different levels of deformability were created by adding non-deformable RBCs (hardened by exposure to 0.08% glutaraldehyde) to the sample of normal healthy RBCs. Ektacytometry indicated a nearly linear decline in RBC deformability with increasing glutaraldehyde concentration. Micropore filtration showed a significant reduction only for concentrations of glutaraldehyde higher than 0.04%. Neither micropore filtration nor ektacytometry measurements could accurately predict the AMVN perfusion. Treatment with diamide reduced RBC deformability as indicated by ektacytometry, but had no significant effect on either micropore filtration or the AMVN perfusion. Both micropore filtration and ektacytometry showed a linear decline in effective RBC deformability with increasing fraction of non-deformable RBCs in the sample. The corresponding decline in the AMVN perfusion plateaued above 50%, reflecting the innate ability of blood flow in the microvasculature to bypass occluded capillaries. Our results suggest that in vitro measurements of RBC deformability performed using either micropore filtration or ektacytometry may not represent the ability of same RBCs to perfuse microvascular networks. Further development of biomimetic tools for measuring RBC deformability (e.g. the AMVN) could enable a more functionally relevant testing of RBC mechanical properties.
Half-dose enoxaparin vs. full-dose enoxaparin for postoperative bridging therapy in patients after cardiac surgery: Which dose regimen should be preferred?
Authors: Weiss Andreas , Brose Stefan , Ploetze Katrin , Matschke Klaus
Published: December 2019

BACKGROUND: Patients who require oral anticoagulation (OAC) after cardiac surgery due to an increased risk for thromboembolic events should receive bridging therapy with heparin until the INR is in a therapeutic range. For this purpose, unfractionated heparin (UFH) or low molecular weight heparin (LMWH) can be used. Recently published studies have demonstrated the safety and efficiency of therapeutic dose LMWH as bridging anticoagulant in cardiac surgery. The present study compares a full-therapeutic dose regimen with a half-therapeutic dose regimen of LMWH looking for safety and efficiency. PATIENTS AND METHODS: This study represents a retrospective, single-center cohort study. In a period of 19 months all patients in whom a postoperative bridging therapy after cardiac surgery was necessary (atrial fibrillation, mechanical heart valve replacement, tricuspid valve repair, intracardiac patch implantation, excision of intracardiac tumors) were selected. In the first part of the study, patients received full-dose (FD = 1 mg/kg bodyweight twice daily) LMWH (Enoxaparin). Analogously, patients in the second part of the study were treated with half-dose (HD = 0.5 mg/kg bodyweight twice daily) LMWH. In case of renal insufficiency (GFR <30 ml/min) the dose was adjusted to one daily application. The duration of follow-up was the patients' entire stay in hospital. Main outcome parameters were bleeding, thromboembolic events, and death. The first dose of LMWH was given on the morning of the first postoperative day, considered that the bleeding risk was acceptable. OAC (Phenprocoumon) was started on the evening of the first postoperative day. RESULTS: Altogether 402 out of 3133 patients met the inclusion criteria (201 patients in each group). Despite a reduced renal function in the HD-group (p = 0.002) both groups were well matched. Mortality was significantly higher in the HD-group than in the FD-group (5.5% vs. 0.5%, p = 0.003) but not related to the anticoagulation regimen. We observed more bleeding events in the FD-group (11 vs. 5, p = 0.126) but vice versa more thromboembolic events in the HD-group (9 vs. 5, p = 0.277). In the HD-group postoperative dialysis was required more often (29 vs. 12, p = 0.011) and there was a higher incidence of patients who were psychic disorientated (42 vs. 26, p = 0.033). The hospital stay was longer in the FD-group (FD: 15.1 ± 9.3 days, HD 12.5 ± 8.1 days, p = 0.003). CONCLUSION: This study shows that a bridging therapy with LMWH is feasible and safe no matter which dose-regimen is used. The differences observed seem not to be related to the anticoagulation. The decision of using a full-dose or half-dose LMWH bridging regimen should be determined by the individual risk of the patient and the general bleeding risk of the procedure.
Evaluation of microvascularization in focal salivary gland lesions by contrast-enhanced ultrasonography (CEUS) and Color Doppler sonography
Authors: Wei Xi , Li Ying , Zhang Sheng , Li Xubin , Wang Hailing , Yong Xu , Wang Xiaoqing , Li Xing , Gao Ming
Published: December 2019

OBJECTIVE: To evaluate the dynamic microvascularization of focal salivary gland lesions by contrast-enhanced ultrasound (CEUS) and Color Doppler sonography. MATERIALS AND METHODS: One hundred and sixty-eight patients with 183 major salivary gland lesions (mean age, 56 years; age range, 12–83 years) underwent gray-scale ultrasonography (US), Color Doppler (CD) and CEUS. The CD and CEUS patterns were classified into three types (scores 0–3). Combined score grades were calculated based on the CD and CEUS pattern scores. The time-intensity curve (TIC) parameters of CEUS were then analyzed. Sensitivity, specificity, negative predictive value and positive predictive value of combined score grades were also calculated. RESULTS: Among all the lesions, there were 161 in parotid gland, 22 in submandibular gland and 157 lesions were benign and 26 were malignant. For score grades (combined CEUS patterns with CD types), scores 1-2 were graded as benign; scores 3-4 were graded as indetermination-suspicious benign or malignant and scores 5-6 were graded as malignant.score 5-6 and score 1-2 indicated 24 (92.3%) and 135 (85.9%) malignant and benign lesions confirmed pathologically, respectively. The sensitivity and negative predicted value of combined score grades for malignant lesions were 92.3% and 98.5%, respectively. In addition, TIC analysis indicates that PI and AUC in malignant lesions were higher than those in benign lesions (p = 0.04 and 0.02, respectively). CONCLUSION: The combined score grade could be a useful method to assess the macro-and micro-vascularization and to differentiated diagnose benign and malignant lesions in major salivary glands.