The effects of spatial inhomogeneities on flow through the endothelial surface layer

Flow through the endothelial surface layer (the glycocalyx and adsorbed plasma proteins) plays an important but poorly understood role in cell signaling through a process known as mechanotransduction. Characterizing the flow rates and shear stresses throughout this layer is critical for understanding how flow-induced ionic currents, deformations of transmembrane proteins, and the convection of extracellular molecules signal biochemical events within the cell, including cytoskeletal rearrangements, gene activation, and the release of vasodilators. Previous mathematical models of flow through the endothelial surface layer are based upon the assumptions that the layer is of constant hydraulic permeability and constant height. These models also assume that the layer is continuous across the endothelium and that the layer extends into only a small portion of the vessel lumen. Results of these models predict that fluid shear stress is dissipated through the surface layer and is thus negligible near endothelial cell membranes. In this paper, such assumptions are removed, and the resultant flow rates and shear stresses through the layer are described. The endothelial surface layer is modeled as clumps of a Brinkman medium immersed in a Newtonian fluid. The width and spacing of each clump, hydraulic permeability, and fraction of the vessel lumen occupied by the layer are varied. The two-dimensional Navier-Stokes equations with an additional Brinkman resistance term are solved using a projection method. Several fluid shear stress transitions in which the stress at the membrane shifts from low to high values are described. These transitions could be significant to cell signaling since the endothelial surface layer is likely dynamic in its composition, density, and height.     

Kinesio taping influences the mechanical behaviour of the skin of the low back: A possible pathway for functionally relevant effects

Despite claims of functional benefits of kinesio tape application, little mechanistic evidence exists to support physiological pathways to achieve these benefits. As kinesio tape is adhered directly to the skin, it can be supposed that any pathway needs to first achieve effects at this level. To address this, two layers of the skin, the combined epidermis and dermis, as well as the hypodermis were studied. Specifically, -kinematic measures of skin surface stretch and retraction, as well as ultrasound measures of skin thickness, were made along all edges of kinesio tape applied over the low back. Results demonstrated that the more superficial skin layer (combined epidermis and dermis), but not the deeper hypodermis, was significantly stretched (p = .0001) and thinner (p = .0016) at either end of the tape, and significantly retracted (p < .0001) and thicker (p = .0001) along the lateral edges of the tape. These results were partly dependent upon spine posture; skin retraction along the tape edges was only apparent in neutral and flexed (but not extended) spine postures, while skin thinning at the tape ends was only apparent in neutral and extended (but not flexed) spine postures. Hypodermal thickness was not affected by kinesio tape application at any location or in any posture. In summary, measured deformations at the skin surface and within the epidermal and dermal regions provide plausible pathways through which kinesio tape could achieve its claimed benefits.     

The effects of tensile-compressive loading mode and microarchitecture on microdamage in human vertebral cancellous bone

The amount of microdamage in bone tissue impairs mechanical performance and may act as a stimulus for bone remodeling. Here we determine how loading mode (tension vs. compression) and microstructure (trabecular microarchitecture, local trabecular thickness, and presence of resorption cavities) influence the number and volume of microdamage sites generated in cancellous bone following a single overload. Twenty paired cylindrical specimens of human vertebral cancellous bone from 10 donors (47–78 years) were mechanically loaded to apparent yield in either compression or tension, and imaged in three dimensions for microarchitecture and microdamage (voxel size 0.7×0.7×5.0 μm³). We found that the overall proportion of damaged tissue was greater (p=0.01) for apparent tension loading (3.9±2.4%, mean±SD) than for apparent compression loading (1.9±1.3%). Individual microdamage sites generated in tension were larger in volume (p<0.001) but not more numerous (p=0.64) than sites in compression. For both loading modes, the proportion of damaged tissue varied more across donors than with bone volume fraction, traditional measures of microarchitecture (trabecular thickness, trabecular separation, etc.), apparent Young?s modulus, or strength. Microdamage tended to occur in regions of greater trabecular thickness but not near observable resorption cavities. Taken together, these findings indicate that, regardless of loading mode, accumulation of microdamage in cancellous bone after monotonic loading to yield is influenced by donor characteristics other than traditional measures of microarchitecture, suggesting a possible role for tissue material properties.     

Bone tissue engineering: the role of interstitial fluid flow

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.     

Free body analysis,beam mechanics,and finite element modeling of the mandible of Alligator mississippiensis

The mechanical behavior of mammalian mandibles is well‐studied, but a comprehensive biomechanical analysis (incorporating detailed muscle architecture, accurate material properties, and three‐dimensional mechanical behavior) of an extant archosaur mandible has never been carried out. This makes it unclear how closely models of extant and extinct archosaur mandibles reflect reality and prevents comparisons of structure–function relationships in mammalian and archosaur mandibles. We tested hypotheses regarding the mechanical behavior of the mandible of Alligator mississippiensis by analyzing reaction forces and bending, shear, and torsional stress regimes in six models of varying complexity. Models included free body analysis using basic lever arm mechanics, 2D and 3D beam models, and three high‐resolution finite element models of the Alligator mandible, incorporating, respectively, isotropic bone without sutures, anisotropic bone with sutures, and anisotropic bone with sutures and contact between the mandible and the pterygoid flange. Compared with the beam models, the Alligator finite element models exhibited less spatial variability in dorsoventral bending and sagittal shear stress, as well as lower peak values for these stresses, suggesting that Alligator mandibular morphology is in part designed to reduce these stresses during biting. However, the Alligator models exhibited greater variability in the distribution of mediolateral and torsional stresses than the beam models. Incorporating anisotropic bone material properties and sutures into the model reduced dorsoventral and torsional stresses within the mandible, but led to elevated mediolateral stresses. These mediolateral stresses were mitigated by the addition of a pterygoid‐mandibular contact, suggesting important contributions from, and trade‐offs between, material properties and external constraints in Alligator mandible design. Our results suggest that beam modeling does not accurately represent the mechanical behavior of the Alligator mandible, including important performance metrics such as magnitude and orientation of reaction forces, and mediolateral bending and torsional stress distributions. J.Morphol. 2011. © 2011 Wiley‐Liss, Inc.     

Articular area responses to mechanical loading: effects of exercise, age, and skeletal location.

How reliable are reconstructions of body mass and joint function based on articular surface areas? While the dynamic relationship between mechanical loading and cross‐sectional geometry in long bones is well‐established, the effect of loading on the subchondral articular surface area of epiphyses (hereafter, articular surface area, or ASA) has not been experimentally tested. The degree to which ASA can change in size and shape is important, because articular dimensions are frequently used to estimate body mass and positional behavior in fossil species. This study tests the hypothesis that mechanical loading influences ASA by comparing epiphyses of exercised and sedentary sheep from three age categories: juvenile, subadult, and adult (n = 44). ASA was measured on latex molds of subchondral articular surfaces of 10 epiphyses from each sheep. Areas were standardized by body mass, and compared to diaphyseal cross‐sectional geometrical data. Nonparametric statistical comparisons of exercised and control individuals found no increases in ASA in response to mechanical loading in any age group. In contrast, significant differences in diaphyseal cross‐sectional geometry were detected between exercised and control groups, but mostly in juveniles. The conservatism of ASA supports the hypothesis that ASA is ontogenetically constrained, and related to locomotor behavior at the species level and to body mass at the individual level, while variations in diaphyseal cross‐sectional geometry are more appropriate proxies for individual variations in activity level. Am J Phys Anthropol 116:266–277, 2001. © 2001 Wiley‐Liss, Inc.     

The effects of insulin on glucose and fluid transport in the isolated small intestine of normal rats

Chronically administered insulin returns enhanced maximal glucose transport capacity induced by diabetes to its normal state. In this study, the direct and acute effects of insulin on glucose transport in different parts of isolated small intestine were investigated. Mucosal Fluid Transport (MFT), Mucosal Glucose Transport (MGT) and Serosal Glucose Transport (SGT) were measured in the presence and absence of insulin in averted sacs, prepared from female Wistar rats. This study shows that the presence of insulin in vitro (40 and 80 microU/mL) can reduce MGT and SGT in different segments of the small intestine (duodenum, jejunum and ileum) after 30 min whereas it had no effect on MFT. Mucosal glucose transfer rates in the duodenum, jejunum and ileum of the controls were 6.07+/-0.4, 6.34+/-0.62 and 6.43+/-0.47 mg/g tissue respectively which were significantly reduced to 3.82+/-0.93, 3.60+/-0.50 and 1.17+/-0.45 in the presence of 80 microU/mL of insulin. Serosal glucose transfer too was decreased significantly from 0.3+/-0.05, 0.57+/-0.07 and 0.43+/-.07 in the duodenum, jejunum and ileum to 0.16+/-0.03, 0.16+/-0.04 and .07+/-.02 respectively. Mucosal fluid transfer was not affected by insulin. Insulin was as effective whether it was added on the mucosal or the serosal side. The results of this study show that insulin can directly affect glucose transport in the small intestine; its physiological role must be examined. Direct effect of insulin deficiency on glucose absorption in diabetic patients may play a role in the pathophysiology of the disease.     

Haemodynamics and stresses in abdominal aortic aneurysms: A fluid-structure interaction study into the effect of proximal neck and iliac bifurcation angle

Our knowledge of how geometry influences abdominal aortic aneurysm (AAA) biomechanics is still developing. Both iliac bifurcation angle and proximal neck angle could impact the haemodynamics and stresses within AAA. Recent comparisons of the morphology of ruptured and intact AAA show that cases with large iliac bifurcation angles are less likely to rupture than those with smaller angles. We aimed to perform fluid-structure interaction (FSI) simulations on a range of idealised AAA geometries to conclusively determine the influence of proximal neck and iliac bifurcation angle on AAA wall stress and haemodynamics.Peak wall shear stress (WSS) and time-averaged WSS (TAWSS) in the AAA sac region only increased when the proximal neck angle exceeded 30°. Both peak WSS (p < 0.0001) and peak von Mises wall stress (p = 0.027) increased with iliac bifurcation angle, whereas endothelial cell activation potential (ECAP) decreased with iliac bifurcation angle (p < 0.001) and increased with increasing neck angle.These observations may be important as AAAs have been shown to expand, develop thrombus and rupture in areas of low WSS. Here we show that AAAs with larger iliac bifurcation angles have higher WSS, potentially reducing the likelihood of rupture. Furthermore, ECAP was lower in AAA geometries with larger iliac bifurcation angles, implying less likelihood of thrombus development and wall degeneration. Therefore our findings could help explain the clinical observation of lower rupture rates associated with AAAs with large iliac bifurcation angles.     

Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis

Shear-mediated platelet activation (SMPA) is central in thrombosis of implantable cardiovascular therapeutic devices. Despite the morbidity and mortality associated with thrombosis of these devices, our understanding of mechanisms operative in SMPA, particularly in free flowing blood, remains limited. Herein we present and discuss a range of emerging mechanisms for consideration for “free flow” activation under supraphysiologic shear. Further definition and manipulation of these mechanisms will afford opportunities for novel pharmacologic and mechanical strategies to limit SMPA and enhance overall implant device safety.     

Principal components analysis of regional bone density in black and white women: relationship to body size and composition.

Black and white women in the United States differ with respect to bone mass and the risk of developing osteoporosis. It has been suggested that greater body size among U.S. blacks may contribute to greater bone density in this group. It is not known whether the fat or lean component contributes more to this relationship. Bone density was measured at seven sites in 161 normal black and white women using single and dual photon absorptiometry. The first principal component accounted for 73% of the variance in the sample and constitutes an index of skeletal mass. The second principal component added another 10% and contrasts the axial and appendicular sites. Both the regional bone densities and the first principal component showed significantly greater bone densities for blacks; adjustment for body size reduced bone mass differences by approximately 50%. Body composition analysis done on a subset of these women indicated that the fat component of body mass may be the more important factor in its effect on bone mass.     

Aging in the musculoskeletal system of rhesus monkeys: III. Bone loss

It is well established that aging of the human skeleton includes the loss of bone mass or density, but little comparative information on age-related osteopenia in other primates is available. In order to determine whether bone loss occurs in normally locomoting nonhuman primates, radiographs of 139 rhesus monkey skeletons from the Cayo Santiago collection were examined, and measures of percent cortical bone (PCT) at the midshaft of second metacarpals, humeri, and femora were calculated. An age-related osteopenia was observed in the metacarpal of adult female macaques, although much individual variation was present. This variability could not be explained by reproductive history (number of offspring), matrilineal affiliation, or degree of osteoarthrosis. However, in a subsample of 15 animals, females who had given birth in the three months prior to death showed lower PCTs than those who had not conceived in the previous mating season. In adult males, PCT did not vary significantly with age, but males that weighed less and those with no/little osteoarthrosis showed lower PCTs than heavier or more arthritic animals, respectively. The multifactorial nature of the variation in PCT observed here suggests that similar processes of bone behavior are involved in the skeletal aging of both humans and rhesus monkeys.     

Modeling evaluation of the fluid-dynamic microenvironment in tissue-engineered constructs: a micro-CT based model

Natural cartilage remodels both in vivo and in vitro in response to mechanical stresses, hence mechanical stimulation is believed to be a potential tool to modulate extra-cellular matrix synthesis in tissue-engineered cartilage. Fluid-induced shear is known to enhance chondrogenesis in engineered cartilage constructs. The quantification of the hydrodynamic environment is a condition required to study the biochemical response to shear of 3D engineered cell systems. We developed a computational model of culture medium flow through the microstructure of a porous scaffold, during direct- perfused culture. The 3D solid model of the scaffold micro-geometry was reconstructed from 250 micro-computed tomography (micro-CT) images. The results of the fluid dynamic simulations were analyzed at the central portions of the fluid domain, to avoid boundary effects. The average, median and mode shear stress values calculated at the scaffold walls were 3.48, 2.90, and 2.45 mPa respectively, at a flow rate of 0.5 cm(3)/min, perfused through a 15 mm diameter scaffold, at an inlet fluid velocity of 53 microm/s. These results were compared to results estimated using a simplified micro-scale model and to results estimated using an analytical macro-scale porous model. The predictions given by the CT-based model are being used in conjunction with an experimental bioreactor model, in order to quantify the effects of fluid-dynamic shear on the growth modulation of tissue-engineered cartilage constructs, to potentially enhance tissue growth in vitro.     

Role of p120-catenin in the morphological changes of endothelial cells exposed to fluid shear stress

p120-Catenin is known to play important roles in cell-cell adhesion stability by binding to cadherin and morphological changes of cells by regulating small RhoGTPase activities. Although the expression and binding states of p120-catenin are thought to dynamically change due to morphological adaptation of endothelial cells (ECs) to fluid shear stress, these dynamics remain to be explored. In the present study, we examined the time course of changes in p120-catenin expression and its binding to vascular endothelial (VE)-cadherin in ECs exposed to shear stress. Human umbilical vein ECs began to change their morphologies at 3-6 h, and became elongated and oriented to the direction of flow at 24 h after exposure to a shear stress of 1.5 Pa. Binding and co-localization of p120-catenin with VE-cadherin at the foci of cell-cell adhesions were retained in ECs during exposure to shear stress, indicating that VE-cadherin was stabilized in the plasma membrane. In contrast, cytoplasmic p120-catenin that was dissociated from VE-cadherin was transiently increased at 3-6 h after the flow onset. These results suggest that the transient increase of cytoplasmic p120-catenin may stimulate RhoGTPase activities and act as a switch for the morphological changes in ECs in response to shear stress.     

Flight performance in the altricial zebra finch: Developmental effects and reproductive consequences

The environmental conditions animals experience during development can have sustained effects on morphology, physiology, and behavior. Exposure to elevated levels of stress hormones (glucocorticoids, GCs) during development is one such condition that can have long‐term effects on animal phenotype. Many of the phenotypic effects of GC exposure during development (developmental stress) appear negative. However, there is increasing evidence that developmental stress can induce adaptive phenotypic changes. This hypothesis can be tested by examining the effect of developmental stress on fitness‐related traits. In birds, flight performance is an ideal metric to assess the fitness consequences of developmental stress. As fledglings, mastering takeoff is crucial to avoid bodily damage and escape predation. As adults, takeoff can contribute to mating and foraging success as well as escape and, thus, can affect both reproductive success and survival. We examined the effects of developmental stress on flight performance across life‐history stages in zebra finches (Taeniopygia guttata). Specifically, we examined the effects of oral administration of corticosterone (CORT, the dominant avian glucocorticoid) during development on ground‐reaction forces and velocity during takeoff. Additionally, we tested for associations between flight performance and reproductive success in adult male zebra finches. Developmental stress had no effect on flight performance at all ages. In contrast, brood size (an unmanipulated variable) had sustained, negative effects on takeoff performance across life‐history stages with birds from small broods performing better than birds from large broods. Flight performance at 100 days posthatching predicted future reproductive success in males; the best fliers had significantly higher reproductive success. Our results demonstrate that some environmental factors experienced during development (e.g. clutch size) have stronger, more sustained effects than others (e.g. GC exposure). Additionally, our data provide the first link between flight performance and a direct measure of reproductive success.     

环境温度和体内储备物共同影响煤山雀夜间体重的下降(英文)

环境温度和体内储备物水平被认为是鸟类在静止状态下能量利用的重要调节因子(夜间体重降低).然而,以往的研究没有把环境温度和体内储备物对夜间能量维持加以明确的区分.为了研究环境温度是否是为煤山雀(Periparus ater)夜间体重调节的直接因子,在自由取食条件下,实验室控制日-日和日-夜环境温度.温度变化模拟西班牙中部地中海山区秋季日-夜温度的变化.夜间体重取决于黄昏时的体重以及前一天体重的增加值.当前一日白天煤山雀体重增加最大时,记录夜间体重最大降低的比率.然而,环境温度的不可预见性没有影响煤山雀夜间体重降低,可以解释煤山雀内在的生理能量平衡.这些结果提示,当一些环境因子如温度变得不可预见时,鸟类在狭小范围内保持体内储备物     

PIXE study on the effects of parathyroid hormone on elemental content in rat bones

Parathyroid hormone (PTH) has attracted considerable interest as a bone anabolic agent. PTH plays a central role in regulating calcium phosphate metabolism and its increases in production in response to low serum calcium levels. A continuous hypersecretion of PTH, as occurs in primary hyperparathyroidism, leads to bone resorption. In this study, the effect of different doses of parathyroid hormone (PTH) on bone mineral content (BMC) in rats was investigated by particle-induced X-ray emission (PIXE). This study will help in investigating further the toxicity of extremely high doses of PTH on BMC. For this study, PTH at doses of 15, 45, or 135 μg/kg/day were applied to 9-month-old male and female Sprague Dawley (SD) rats. The concentrations of calcium (Ca), phosphorus (P), strontium (Sr), and zinc (Zn) were measured for bone treatment of PTH. From the results of the research, it was revealed that the biomechanical characteristics of the bone as well as the bone mass were enhanced after the treatment. It was further found that the concentrations of other elements also increased, excluding Zn. This research proved that PTH assists in the treatment of osteoporosis as revealed by the characteristics of different elements. PIXE can be used to determine the concentrations of bone mineral content.     

Development of osteological structures in the sea bream: vertebral column and caudal fin complex

The development of cartilaginous structures in cultured sea bream Sparus aurata larvae and the timing of their ossification was studied. In cultivated sea bream larvae the first cartilaginous structure to be identified was hypural 1 at 4.1 mm notochord length ( L _N). By 5.3 mm L _N, prior to the onset of ossification, it was possible to distinguish the following cartilaginous structures: all 23 neural arches, all 13 haemal arches and two of the four pairs of parapophyses. The neural arches 1–4 and 15–23 were formed on the notochord and elongated dorsally, while neural arches 5–14 appeared on the dorsal side of the spinal cord and elongated ventrally. Initiation of ossification occurred at 5.7–6.0 mm standard length ( L _S) when the cartilaginous ontogeny of the vertebral column was completed. Ossification was coincident with dorsal flexion at the posterior end of the notochord and occurred in a sequential manner: (1) dorsoanteriorly, the cartilaginous neural arches and the centra were the first structures to ossify; (2) ventrad at the centre, at 7.0–7.5 mm L _S; (3) posteriorly at 7.1 mm L _S the hypural complex and urostyle (24th centrum) were ossified; and (4) dorsad at the centre (neural arches and spines).