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Osteoarthritic synovial fluid and correlations with protein concentration. 骨关节炎滑液与蛋白浓度的关系。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-01-01 DOI: 10.3233/BIR-15086
A. Madkhali, Michael Chernos, S. Fakhraei, D. Grecov, E. Kwok
BACKGROUND Osteoarthritis is a common, localized joint disease that causes pain, stiffness and reduced mobility. The effects of osteoarthritis on the extensional rheology of synovial fluid in the knees are not fully understood and consequently require further study. OBJECTIVE The purpose of this work is to study the extensional rheology of osteoarthritic synovial fluid and to investigate a possible correlation between synovial fluid protein concentration and extensional rheology. The study will also investigate possible correlations with the shear rheology. METHODS 21 osteoarthritic synovial fluid samples were studied under extensional flow with a capillary breakup extensional rheometer. Extensional rheological properties were correlated with protein concentration and with shear rheological properties measured in a prior study. Viscosupplement was also studied under extensional flow for comparison. RESULTS Extensional rheological properties were found to vary widely between samples, but in general were found to agree with previous studies. No statistically significant correlation was identified between extensional rheological properties and protein concentration. Positive correlations were identified between zero shear viscosity and terminal extensional viscosity (R-squared = 0.73), zero shear viscosity and extensional relaxation time (R-squared = 0.84), and shear relaxation time and extensional relaxation time (R-squared = 0.75). CONCLUSIONS Appropriate CaBER operating parameters for study of osteoarthritic synovial fluid were identified. No statistically significant correlation was found to exist between protein concentration and extensional rheological parameters. Positive correlations were identified between several shear and extensional rheological parameters. The reported values for extensional viscosity and relaxation times for synovial fluid were found to be within one order of magnitude with a recent study of post mortem synovial fluid.
背景:骨关节炎是一种常见的局部关节疾病,可引起疼痛、僵硬和活动能力降低。骨关节炎对膝关节滑液伸展流变的影响尚不完全清楚,因此需要进一步研究。目的研究骨关节炎滑膜液的外延流变性,探讨滑膜液蛋白浓度与外延流变性之间的关系。该研究还将探讨与剪切流变学的可能相关性。方法采用毛细管破裂拉伸流变仪对21例骨关节炎滑膜液进行拉伸流变研究。在先前的研究中,拉伸流变性能与蛋白质浓度和剪切流变性能相关。在拉伸流动条件下进行了粘补充试验,并进行了比较。结果拉伸流变性能发现试样之间的差异很大,但在一般情况下发现与以往的研究一致。拉伸流变特性与蛋白质浓度之间没有统计学上的显著相关性。零剪切粘度与末端拉伸粘度(R-squared = 0.73)、零剪切粘度与拉伸松弛时间(R-squared = 0.84)、剪切松弛时间与拉伸松弛时间(R-squared = 0.75)呈正相关。结论确定了适合骨关节炎滑膜液研究的CaBER操作参数。蛋白浓度与拉伸流变参数之间无统计学意义的相关性。几个剪切和拉伸流变参数之间存在正相关关系。最近对死后滑液的研究发现,滑液的拉伸粘度和松弛时间的报告值在一个数量级内。
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引用次数: 4
Biphasic impairment of erythrocyte deformability in response to repeated, short duration exposures of supraphysiological, subhaemolytic shear stress. 红细胞变形能力的双相损伤响应于重复,短时间暴露的超生理,亚溶血剪切应力。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-01-01 DOI: 10.3233/BIR-15108
Antony P. McNamee, G. Tansley, S. Sabapathy, Michael J. Simmonds
INTRODUCTION Despite current generation mechanical assist devices being designed to limit shear stresses and minimise damage to formed elements in blood, severe secondary complications suggestive of impaired rheological functioning are still observed. At present, the precise interactions between the magnitude-duration of shear stress exposure and the deformability of red blood cells (RBC) remain largely undescribed for repeated subhaemolytic shear stress duty-cycles of less than 15 s. Given that the time taken for blood to traverse mechanical devices (e.g., Bio Pump) typically ranges from 1.85-3.08 s, the present study examined the influence of repeated, short duration, supraphysiological shear stress exposure on RBC function. METHODS RBC were exposed to shear stress duty-cycles of 64 Pa × 3 s or 88 Pa × 2 s, for 10 repeated bouts, in an annular Couette shearing system and ektacytometer. Laser diffractometry was used to measure RBC deformability before and after application of each duty-cycle. Free haemoglobin concentration and RBC morphology was also examined following shear exposure to determine cell viability. RESULTS Initial exposure to shear stress duty-cycles decreased RBC deformability and increased RBC sensitivity to mechanical damage. Interestingly, the pattern of change in these variables reversed and returned to baseline values within two successive duty-cycle exposures. Significant improvements in RBC deformability were then observed by the 9th repeated exposure to 64 Pa × 3 s. CONCLUSIONS Repeat applications of short duration supraphysiological, subhaemolytic shear stress induces a biphasic RBC deformability response that appears to progressively improve initially impaired RBC populations.
尽管当前一代的机械辅助装置旨在限制剪切应力并最大限度地减少对血液中形成元素的损害,但仍然观察到严重的继发性并发症,表明流变功能受损。目前,剪切应力暴露的大小和持续时间与红细胞(RBC)变形能力之间的确切相互作用在很大程度上仍未被描述为小于15 s的重复亚溶血剪切应力占空比。鉴于血液通过机械装置(如生物泵)所需的时间通常在1.85-3.08秒之间,本研究检测了重复、短时间、超生理剪切应力暴露对RBC功能的影响。方法在环形Couette剪切系统和光度计中,连续10次暴露于64 Pa × 3s或88 Pa × 2s的剪切应力占空比下。采用激光衍射法测量各占空比前后红细胞的变形能力。游离血红蛋白浓度和红细胞形态也检查剪切暴露后,以确定细胞活力。结果初始暴露于剪切应力占空比降低了红细胞的变形能力,增加了红细胞对机械损伤的敏感性。有趣的是,在两个连续的占空比暴露中,这些变量的变化模式逆转并返回到基线值。在第9次暴露于64 Pa × 3 s时,红细胞变形能力显著改善。结论:重复应用短时间的生理上、亚溶血剪切应力诱导双期RBC变形性反应,似乎逐步改善最初受损的RBC种群。
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引用次数: 20
Deformation and rupture of Dunaliella salina at high shear rates without the use of thickeners. 不使用增稠剂的盐杜氏藻在高剪切速率下的变形和破裂。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-01-01 DOI: 10.3233/BIR-15057
D. Kokkinos, H. Dakhil, A. Wierschem, H. Briesen, A. Braun
BACKGROUND High-density cultures require operating below the critical threshold of shear stress, in order to avoid reducing the specific growth rate of the cells. When determining this threshold, direct inspection of the cells in flow provides insight into the conditions of shearing. OBJECTIVE Aim of this study was using a novel rheo-optical setup for the observation of cells in laminar shear flow and the determination of the critical shear stress required to damage them in their natural environment. METHODS Dunaliella salina cells were sheared and observed in flow for shear stresses of up to 90 Pa, at ambient temperature, without adding thickeners. The critical shear stress was determined by fitting a hydrodynamics-based criterion to the experimental data on the percentage of deformed cells after shearing. RESULTS Single cells, clusters and strings of cells were visible in shear flow. The strings formed at maximum shear stresses of 10 Pa or higher. Cells lost motility for maximum shear stresses higher than 15 Pa, and more than 80% of the cells were deformed at maximum shear stresses higher than 60 Pa. The estimated critical shear stress was 18 Pa. CONCLUSIONS Shear stresses higher than 18 Pa should be avoided when cultivating D. salina.
为了避免降低细胞的特定生长速率,高密度培养需要在剪切应力的临界阈值以下操作。当确定这个阈值时,直接检查流动中的细胞可以深入了解剪切条件。目的利用一种新型的流变光学装置观察细胞在层流剪切流中的状态,并测定细胞在自然环境中受到破坏所需的临界剪切应力。方法在不添加增稠剂的情况下,将盐藻细胞在室温下,在高达90pa的剪切应力下进行剪切和观察。临界剪切应力是通过将基于流体力学的准则拟合到剪切后变形细胞百分比的实验数据中来确定的。结果剪切流中可见单细胞、细胞簇和细胞串。在10pa或更高的最大剪切应力下形成的弦。当最大剪应力大于15 Pa时,细胞失去运动能力,超过80%的细胞在最大剪应力大于60 Pa时发生变形。估计临界剪应力为18 Pa。结论培养盐藻时应避免剪应力大于18 Pa。
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引用次数: 6
Role of fluid shear stress in regulating VWF structure, function and related blood disorders 流体剪切应力在调节VWF结构、功能和相关血液疾病中的作用
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2015-11-19 DOI: 10.3233/BIR-15061
Shobhit Gogia, S. Neelamegham
Von Willebrand factor (VWF) is the largest glycoprotein in blood. It plays a crucial role in primary hemostasis via its binding interaction with platelet and endothelial cell surface receptors, other blood proteins and extra-cellular matrix components. This protein is found as a series of repeat units that are disulfide bonded to form multimeric structures. Once in blood, the protein multimer distribution is dynamically regulated by fluid shear stress which has two opposing effects: it promotes the aggregation or self-association of multiple VWF units, and it simultaneously reduces multimer size by facilitating the force-dependent cleavage of the protein by various proteases, most notably ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type repeats, motif 1 type 13). In addition to these effects, fluid shear also controls the solution and substrate-immobilized structure of VWF, the nature of contact between blood platelets and substrates, and the biomechanics of the GpIbα–VWF bond. These features together regulate different physiological and pathological processes including normal hemostasis, arterial and venous thrombosis, von Willebrand disease, thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome. This article discusses current knowledge of VWF structure–function relationships with emphasis on the effects of hydrodynamic shear, including rapid methods to estimate the nature and magnitude of these forces in selected conditions. It shows that observations made by many investigators using solution and substrate-based shearing devices can be reconciled upon considering the physical size of VWF and the applied mechanical force in these different geometries.
血管性血友病因子(VWF)是血液中最大的糖蛋白。它通过与血小板和内皮细胞表面受体、其他血液蛋白和细胞外基质成分的结合相互作用,在原发性止血中起着至关重要的作用。这种蛋白质被发现为一系列重复单元,它们是二硫键结合形成多聚体结构的。一旦进入血液,蛋白质多聚体的分布受到流体剪切应力的动态调节,流体剪切应力具有两种相反的作用:它促进多个VWF单元的聚集或自结合,同时通过促进各种蛋白酶对蛋白质的力依赖性切割来减少多聚体的大小,最明显的是ADAMTS13(一种具有血栓反应蛋白型重复序列的崩解素和金属蛋白酶,motif 1 type 13)。除了这些影响外,流体剪切还控制着VWF的溶液和底物固定结构,血小板与底物之间的接触性质,以及GpIbα-VWF键的生物力学。这些特征共同调节着正常止血、动脉和静脉血栓形成、血管性血友病、血栓性血小板减少性紫癜和获得性血管性血友病等不同的生理和病理过程。本文讨论了目前关于VWF结构-功能关系的知识,重点是水动力剪切的影响,包括在选定条件下估计这些力的性质和大小的快速方法。这表明,考虑到VWF的物理尺寸和在这些不同几何形状下施加的机械力,许多研究人员使用溶液和基材剪切装置所做的观察可以协调一致。
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引用次数: 78
15th International Congress of Biorheology and 8th International Conference on Clinical Hemorheology, Seoul, Korea, May 24-28, 2015: Scientific Program. 第15届国际生物流变学大会和第8届国际临床血液流变学会议,韩国首尔,2015年5月24-28日:科学计划。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2015-01-01 DOI: 10.3233/BIR-150669
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引用次数: 0
Hemodynamics in stenotic vessels of small diameter under steady state conditions: Effect of viscoelasticity and migration of red blood cells. 稳态条件下小直径狭窄血管的血流动力学:红细胞粘弹性和迁移的影响。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2015-01-01 DOI: 10.3233/BIR-14033
Yannis Dimakopoulos, George Kelesidis, Sophia Tsouka, Georgios C Georgiou, John Tsamopoulos
BACKGROUND In microcirculation, the non-Newtonian behavior of blood and the complexity of the microvessel network are responsible for the high flow resistance and the large reduction of the blood pressure. Red blood cell aggregation along with inward radial migration are two significant mechanisms determining the former. Yet, their impact on hemodynamics in non-straight vessels is not well understood. OBJECTIVE In this study, the steady state blood flow in stenotic rigid vessels is examined, employing a sophisticated non-homogeneous constitutive law. The effect of red blood cells migration on the hydrodynamics is quantified and the constitutive model's accuracy is evaluated. METHODS A numerical algorithm based on the two-dimensional mixed finite element method and the EVSS/SUPG technique for a stable discretization of the mass and momentum conservation equations in addition to the constitutive model is employed. RESULTS The numerical simulations show that a cell-depleted layer develops along the vessel wall with an almost constant thickness for slow flow conditions. This causes the reduction of the drag force and the increase of the pressure gradient as the constriction ratio decreases. CONCLUSIONS Viscoelastic effects in blood flow were found to be responsible for steeper decreases of tube and discharge hematocrits as decreasing function of constriction ratio.
背景:在微循环中,血液的非牛顿行为和微血管网络的复杂性是高流动阻力和血压大幅降低的原因。红细胞聚集和向内径向迁移是决定前者的两个重要机制。然而,它们对非直血管血流动力学的影响尚不清楚。目的:在本研究中,采用复杂的非均匀本构法检查狭窄刚性血管的稳态血流。定量分析了红细胞迁移对流体力学的影响,并评价了本构模型的准确性。方法:采用基于二维混合有限元法和EVSS/SUPG技术的数值算法,在本构模型的基础上对质量守恒方程和动量守恒方程进行稳定离散。结果:数值模拟结果表明,在慢流条件下,沿血管壁形成了一层厚度几乎恒定的细胞耗尽层。随着收缩比的减小,阻力减小,压力梯度增大。结论:血流中的粘弹性效应是导致管腔和放电红细胞压积以收缩比递减的主要原因。
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引用次数: 29
Hemodynamics of the renal artery ostia with implications for their structural development and efficiency of flow. 肾动脉口的血流动力学及其结构发育和血流效率的影响。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2015-01-01 DOI: 10.3233/BIR-15069
W. McIntosh, M. Ozturk, L. A. Down, D. Papavassiliou, E. O’Rear
BACKGROUND Energy losses at tube or blood vessel orifices depend on the extent of flare as measured by the dimensionless ratio of the fillet radius of curvature to diameter (r/D). OBJECTIVE The goal of this study was to assess the effect of ostial fillet radii on energy losses at the aorta-renal artery junctions since as much as a quarter of cardiac output passes through the kidneys. METHOD Pressure loss coefficients K for the renal artery ostia as a function of r/D have been determined for representative anatomical variants using finite volume simulations. Estimates of fillet radii in humans from image analysis were employed in simulations for comparison of loss coefficients. RESULTS Values for K drop 45% as r/D increases over the range 0-1.3. Image analysis indicates that the ostia are not symmetric in humans with (r/D)superior much larger than (r/D)inferior. Simulations show the loss coefficient depends almost entirely on the superior fillet radius. CONCLUSIONS Superior fillet radii for both renal arteries are similar to the optimal value to reduce energy losses while the inferior radii are not. Ostial asymmetry may have been induced by higher levels of shear stress present on the superior portion of a developing symmetric ostium of small r/D.
背景:管道或血管孔处的能量损失取决于通过圆角曲率半径与直径的无量纲比(r/D)测量的耀斑程度。目的:本研究的目的是评估口角半径对主动脉-肾动脉交界处能量损失的影响,因为多达四分之一的心输出量通过肾脏。方法通过有限体积模拟,确定了肾动脉开口压力损失系数K作为r/D的函数。从图像分析中估计的人体圆角半径被用于模拟损失系数的比较。结果在0-1.3范围内,随着r/D的增加,K值下降45%。图像分析表明,人类的口不对称,上口(r/D)远大于下口(r/D)。仿真结果表明,损耗系数几乎完全取决于优越的圆角半径。结论两肾动脉的上角半径与减少能量损失的最优值相近,而下角半径则不同。小r/D发育的对称口的上部存在较高水平的剪切应力,可能导致了口不对称。
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引用次数: 1
Using cell monolayer rheology to probe average single cell mechanical properties. 利用细胞单层流变学研究平均单细胞力学性能。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2015-01-01 DOI: 10.3233/BIR-15070
M. Sander, J. Flesch, A. Ott
The cell monolayer rheology technique consists of a commercial rotational rheometer that probes the mechanical properties of a monolayer of isolated cells. So far we have described properties of an entire monolayer. In this short communication, we show that we can deduce average single cell properties. Results are in very good agreement with earlier work on single cell mechanics. Our approach provides a mean of 105-106 adherent cells within a single experiment. This makes the results very reproducible. We extend our work on cell adhesion strength and deduce cell adhesion forces of fibroblast cells on fibronectin coated glass substrates.
细胞单层流变学技术由一个商业旋转流变仪组成,该流变仪探测分离细胞单层的机械特性。到目前为止,我们已经描述了整个单层的性质。在这个简短的交流中,我们展示了我们可以推断出平均单细胞的性质。结果与早期的单细胞力学工作非常吻合。我们的方法在单个实验中平均提供105-106个贴壁细胞。这使得结果非常具有可重复性。我们扩展了细胞粘附强度的研究,并推导了成纤维细胞在纤维连接蛋白涂层玻璃基板上的粘附力。
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引用次数: 6
Influence of plaque stiffness on deformation and blood flow patterns in models of stenosis. 斑块硬度对狭窄模型中变形和血流模式的影响。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2015-01-01 DOI: 10.3233/BIR-14016
Yasutomo Shimizu, Makoto Ohta

Background: Blood flow in stenotic vessels strongly influences the progression of vascular diseases. Plaques in stenotic blood vessels vary in stiffness, which influences plaque behavior and deformation by pressure and flow. Concurrent changes in plaque geometry can, in turn, affect blood flow conditions. Thus, simultaneous studies of blood flow and plaque deformation are needed to fully understand these interactions.

Objectives: This study aims to identify the change of flow conditions attendant to plaque deformation in a model stenotic vessel.

Methods: Three plaques of differing stiffness were constructed on a vessel wall using poly (vinyl alcohol) hydrogels (PVA-H) with defined stiffness to facilitate simultaneous observations of blood flow and plaque deformation. Flow patterns were observed using particle image velocimetry (PIV).

Results: Decreases in Reynolds number (Re) with increased plaque deformation suggest that velocity decrease is more critical to establishment of the flow pattern than expansion of the model lumen. Upon exiting the stenosis, the location of the flow reattachment point, shifted further downstream in all models as plaque stiffness decreased and depended on the increase in upstream pressure.

Conclusions: These results suggest that in addition to luminal area, plaque stiffness should be considered as a measure of the severity of the pathology.

背景:狭窄血管的血流严重影响血管疾病的进展。狭窄血管中的斑块硬度不同,这影响斑块的行为和变形。斑块几何形状的同时变化反过来会影响血流状况。因此,需要同时研究血流和斑块变形,以充分了解这些相互作用。目的:本研究旨在确定模型狭窄血管斑块变形时血流条件的变化。方法:使用具有一定硬度的聚乙烯醇水凝胶(PVA-H)在血管壁上构建三个不同硬度的斑块,以方便同时观察血流和斑块变形。用粒子图像测速仪(PIV)观察流动模式。结果:随着斑块变形的增加,雷诺数(Re)降低,表明流速的降低比模型管腔的膨胀对流型的建立更为关键。在所有模型中,离开狭窄后,血流再附着点的位置随着斑块刚度的降低而进一步向下游移动,并依赖于上游压力的增加。结论:这些结果表明,除了管腔面积外,斑块硬度应被视为病理严重程度的衡量标准。
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引用次数: 10
Numerical simulation of dielectrophoretic separation of live/dead cells using a three-dimensional nonuniform AC electric field in micro-fabricated devices. 微加工器件中三维非均匀交流电场对活/死细胞介电泳分离的数值模拟。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2015-01-01 DOI: 10.3233/BIR-14039
Shigeru Tada

Background: The analysis of cell separation has many important biological and medical applications. Dielectrophoresis (DEP) is one of the most effective and widely used techniques for separating and identifying biological species.

Objective: In the present study, a DEP flow channel, a device that exploits the differences in the dielectric properties of cells in cell separation, was numerically simulated and its cell-separation performance examined.

Methods: The samples of cells used in the simulation were modeled as human leukocyte (B cell) live and dead cells. The cell-separation analysis was carried out for a flow channel equipped with a planar electrode on the channel's top face and a pair of interdigitated counter electrodes on the bottom. This yielded a three-dimensional (3D) nonuniform AC electric field in the entire space of the flow channel.

Results: To investigate the optimal separation conditions for mixtures of live and dead cells, the strength of the applied electric field was varied. With appropriately selected conditions, the device was predicted to be very effective at separating dead cells from live cells.

Conclusions: The major advantage of the proposed method is that a large volume of sample can be processed rapidly because of a large spacing of the channel height.

背景:细胞分离分析具有许多重要的生物学和医学应用。Dielectrophoresis (DEP)是分离和鉴定生物物种最有效、应用最广泛的技术之一。目的:对利用细胞介电特性差异进行分离的DEP流道进行了数值模拟,并对其分离性能进行了研究。方法:采用人白细胞(B细胞)活细胞和死细胞模型进行模拟。对在流道顶部安装一个平面电极,在流道底部安装一对互指反电极的流道进行了细胞分离分析。这在整个流道空间中产生了三维(3D)非均匀交流电场。结果:在不同的外加电场强度下,研究了活细胞和死细胞混合物的最佳分离条件。在适当选择的条件下,预计该装置在分离死细胞和活细胞方面非常有效。结论:该方法的主要优点是通道高度间距大,可快速处理大量样品。
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引用次数: 6
期刊
Biorheology
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