bluuebunny/crossref_metadata_2025 huggingface dataset:
Revision of the genus Calyxochaetus Bigot (Diptera: Dolichopodidae: Sympycninae)
Authors: RUNYON JUSTIN B.
Published: November 2024

The New World genus Calyxochaetus Bigot (Diptera: Dolichopodidae) is revised and 36 species are recognized, including 14 new species. These species are classified into five species groups as follows: the C. tripilus species group including C. angustipennis (Aldrich, 1901) comb. nov., C. longitarsus sp. nov. and C. tripilus (Van Duzee, 1930); the C. cilifemoratus species group including C. anisoaristus sp. nov., C. arizonicus (Harmston, 1968), C. brooksi sp. nov., C. celatus sp. nov., C. cilifemoratus (Van Duzee, 1924), C. clavicornis (Van Duzee, 1930), C. coloradensis sp. nov., C. distortus (Van Duzee, 1930), C. hardyi (Harmston & Knowlton, 1940), C. harmstoni sp. nov., C. isoaristus (Harmston & Knowlton, 1940), C. luteipes (Van Duzee, 1923) and C. syilx sp. nov.; the C. fortunatus species group including C. cascadia sp. nov., C. fortunatus (Wheeler, 1899), C. leptofortunatus sp. nov., C. oreas (Wheeler, 1899) and C. vegetus (Wheeler, 1899); the C. insolitus species group including C. insolitus (Van Duzee, 1932) and C. pennarista (Harmston & Knowlton, 1940); and the C. frontalis species group including C. binodatus (Harmston & Knowlton, 1940), C. bovanodatus sp. nov., C. desertus sp. nov., C. frontalis (Loew, 1861), C. furcatus (Van Duzee, 1929), C. lamellicornis Parent, 1930, C. lacrima sp. nov., C. nodatus (Loew, 1862), C. ornatus Parent, 1930, C. pictipes (Harmston & Knowlton, 1940), C. remifer sp. nov., C. sobrinus (Wheeler, 1899) and C. tohono sp. nov. The following seven new synonyms are proposed: Calyxochaetus metatarsalis Robinson, 1966 = C. tripilus, syn. nov.; C. millardi Meuffels & Grootaert, 1999 = C. distortus, syn. nov.; C. unipilus (Van Duzee, 1929) = C. furcatus, syn. nov.; C. loewii Parent, 1930 = C. furcatus, syn. nov.; C. patellifer Parent, 1934 = C. ornatus, syn. nov.; C. inornatus (Van Duzee, 1917) = C. sobrinus, syn. nov. and C. hastatus (Van Duzee, 1930) = C. sobrinus, syn. nov. Lectotype designations are made for C. angustipennis, C. frontalis, C. inornatus, C. nodatus and C. vegetus. The known distribution of each species is mapped and a key to males is provided.
Determination of the content of nonfilterable cells in erythrocyte suspensions as a function of the medium osmolality
Authors: Lisovskaya I.L. , Shurkhina E.S. , Nesterenko V.M. , Rozenberg J.M. , Ataullakhanov F.I.
Published: November 2024

The results of most filtration assays for deformability of erythrocytes do not distinguish whether the entire population or only its small fraction exhibits abnormal rheological properties. We developed a simple filtration method for determination of the percentage of nonfilterable cells in erythrocyte suspension using membrane filters with mean pore diameter of 3.1 $\mu$ m. This method makes it possible to detect even minor abnormal subpopulations in erythrocyte suspensions. The flow rate of buffer depends on the number of free pores of a filter. The plot of the number of pores clogged by nonfilterable cells vs the total number of erythrocytes that were allowed to pass through the filter had a linear portion, with a slope representing the relative content, $Z$ %, of nonfilterable cells in the suspension. We determined $Z$ % for various medium osmolalities $u$ and used the data to derive the distribution of erythrocytes in $u_{\mathrm{cr}}$ ( $u_{\mathrm{cr}}$ is the maximum value of $u$ at which an erythrocyte cannot pass through a pore of a given filter because of geometric limitations). The distribution of $u_{\mathrm{cr}}$ in suspension of normal erythrocytes has a maximum of about 200 mOsm/kg and a half‐width of about 20 mOsm/kg. The distributions of $u_{\mathrm{cr}}$ are altered in normal erythrocyte suspensions at decreased pH values, in cryopreserved and ATP‐depleted erythrocyte suspensions and in erythrocytes from a xerocytosis patient.
Complex viscoelasticity of normal and lectin treated erythrocytes using laser diffractometry
Authors: Riquelme B.D. , Valverde J. , Rasia R.J.
Published: November 2024

A new method to find directly complex viscoelastic parameters (CVP) of red blood cells (RBC) is presented in this paper. Experimental determinations were carried out in an Erythrodeformeter (Rasia et al., 1986) operating in oscillating mode (0.5 to 3.5 Hz). The Erythrodeformeter performs direct determination of CVP of erythrocytes undergoing sinusoidal shear stresses by laser diffractometry. The measurements lead to the determination of mean values of the four components of erythrocyte complex viscoelasticity. The influence of the alterations induced on erythrocyte membrane by vegetable lectins (Ulex europaeus, wheat germ agglutinin and Enterolobium contorticilicum seeds) was analyzed to verify the sensitivity of this method. Differences observed between the CVP parameters of treated cells and the ones corresponding to control samples (non treated cells) are analyzed. Results obtained from cells treated with wheat germ agglutinin agree with observations published by Smith and Hochmuth (1982). Determinations of RBC complex viscoelasticity carried out by laser diffractometry could become an important tool to understand the influence of the factors associated with alterations of the rheologic properties of RBC membrane, which can affect the in vivo blood flow.
Bioelectrorheological model of the cell. 8. Cellular deformation under prolonged and recurrent shear stress
Authors: Pawłowski P. , Fikus M.
Published: November 2024

The influence of a prolonged and recurrent shear stress created by a periodic electric field on the mechanical properties of Neurospora crassa cells was investigated. Conditions were found under which modifications of cellular structures responding to stress become irreversible, and plastic flow of the viscoelastic structural elements is observed. The symmetry of the response of the cell under stress application and relaxation was lost, when compared to the reference conditions. To interpret the results a general rheological model was proposed. As previously described (Pawłowski et al., 1997), the existence of the three hypothetical supramolecular regions of the membrane (F, S and 0) was suggested. Rheological parameters for the above regions were calculated. Theoretical functions were satisfactorily fitted to the experimental results.
A new capillary viscometer for whole blood viscosimetry
Authors: Marinakis G.N. , Barbenel J.C. , Fisher A.C. , Tsangaris S.G.
Published: November 2024

A new capillary system was developed, incorporating infrared sensors, which allowed the determination of whole blood viscosity over a wide range of shear stresses. Flow conditions were defined by the geometry of the capillary and the sample pressure head. Whole blood was considered to be a power law fluid and a modified Mooney’s formula was used for the calculation of the related invariants. The new viscometer proved to be very simple in use, requiring one run, had a short measuring time and utilised a small test sample volume. However it can be used for whole blood viscosity measurements only at medium and high shear stresses.
Adhesion of nonmetastatic and highly metastatic breast cancer cells to endothelial cells exposed to shear stress
Authors: Summers Moss Melissa , Sisken Betty , Zimmer Steve , Anderson Kimberly W.
Published: November 2024

The mechanical stimulus of shear stress has to date been neglected when studying the adhesion of cancer cells to the endothelium. Confluent monolayers of endothelial cells were subjected to either 4 or 15 hours of arterial shear stress. Adhesion of nonmetastatic (MCF‐7) and highly metastatic (MDA‐MB‐435) human breast cancer cells was then quantified using a detachment assay carried out inside the parallel plate flow chamber. Four hours of shear stress exposure had no effect on adhesion. However, 15 hours of shear stress exposure led to marked changes in the ability of the endothelial monolayer to bind human breast cancer cells. An increase in adhesive strength was observed for nonmetastatic MCF‐7 cells, while a decrease in adhesive strength was observed for highly metastatic MDA‐MB‐435 cells. Hence, endothelial shear stress stimulation does influence the adhesion of cancer cells to the endothelium and can have different effects on the adhesion of cancer cells with different metastatic potentials. Furthermore, adhesion of nonmetastatic and highly metastatic human breast cancer cells may be controlled by two different endothelial cell adhesion molecules that are differentially regulated by shear stress. Immunohistochemistry confirmed that shear stress did in fact differentially regulate endothelial cell adhesion molecule expression.
Present perspectives on cartilage and chondrocyte mechanobiology
Authors: Urban J.P.G.
Published: November 2024

The focus of work on mechanotransduction in cartilage has changed markedly over the last 10 years. At the beginning of the decade, the interest lay in determining the net response of cartilage plugs, almost always as $^{35}$ S‐sulphate or $^{3}$ H‐proline incorporation, to a variety of external loads, with the focus on whether changes in frequency in particular would stimulate or inhibit proteoglycan and protein synthesis . Over the past few years the emphasis has shifted; it is now based mainly at the level of the cell as illustrated in Fig. 1. Here we will present a brief overview of the work presented at this symposium in light of these changes in approach.
Cell mechanotransduction and interactions with biological tissues
Authors: Oddou C. , Wendling S. , Petite H. , Meunier A.
Published: November 2024

The biomechanical mechanisms involved in the processes of tissue remodeling and adaptation are reviewed with emphasis on mechanotransduction at the cellular level. New theoretical models associated with experimental rheological techniques are briefly commented.
Molecular biology and self‐regulatory mechanisms of blood viscosity: A review
Authors: Reinhart Walter H.
Published: November 2024

Blood viscosity is determined by plasma viscosity, hematocrit, erythrocyte deformability and aggregation. Plasma viscosity and hematocrit are directly regulated by the organism. The molecular biology of the principal determinants of plasma viscosity, i.e., fibrinogen, immunoglobulins, albumin, and lipoproteins is outlined in this work. Hematocrit is regulated by erythropoietin, which is primarily induced by tissue hypoxia. Evidence begins to emerge that autoregulatory mechanisms may be involved in blood viscosity. Viscosity modulates gene transcription for albumin and apolipoproteins in cultured hepatocytes and the erythropoietin response to anemia in rats. Further investigations into these self‐regulatory mechanisms in biorheology are, however, needed for a better understanding of blood viscosity regulation in health and disease.
A role for β2 integrin (CD11/CD18)‐mediated tyrosine signaling in extravasation of human polymorphonuclear neutrophils
Authors: Willeke Thomas , Scharffetter‐Kochanek Karin , Gaehtgens Peter , Walzog Barbara
Published: November 2024

During the recruitment of human polymorphonuclear neutrophils (PMN) to sites of inflammation, leukocyte adhesion molecules of the β2 integrin (CD11/CD18) family mediate firm adhesion of these cells to the endothelial cell monolayer lining the vessel wall. This process is a prerequisite for shape change and spreading of PMN on the endothelium which eventually allows PMN emigration into the extravascular space. In order to elucidate the molecular mechanisms which mediate this sequence of events, intracellular protein tyrosine signaling was studied subsequent to β2 integrin‐mediated ligand binding. Using western blotting technique, β2 integrin‐mediated adhesion was found to induce tyrosine phosphorylation of different proteins. The effect was absent in PMN derived from CD18‐deficient mice which lack any β2 integrin expression on the cell surface demonstrating the specificity of the observed response. Inhibition of β2 integrin‐mediated tyrosine signaling by herbimycin A almost completely inhibited adhesion, shape change, and subsequent spreading of PMN. Herbimycin A also diminished chemotactic migration of these cells in response to the soluble mediator N‐formyl‐Met–Leu–Phe (fMLP). In contrast, treatment of PMN with cytochalasin D had no substantial effect on β2 integrin‐mediated signaling or adhesion but inhibited shape change, spreading, and chemotactic migration of PMN. This suggests that the signaling capacity exerted by β2 integrins upon ligand binding was independent of an intact cytoskeleton. Moreover, the β2 integrin‐mediated activation of intracellular signal transduction pathways was critical for firm adhesion of PMN, the prerequisite subsequent shape change and spreading, which allows emigration of PMN into the extravascular space.
Dependence of adhesive behavior of neutrophils on local fluid dynamics in a region with recirculating flow
Authors: Skilbeck Christopher , Westwood Susan M. , Walker Peter G. , David Tim , Nash Gerard B.
Published: November 2024

We have recently described patterns of adhesion of different types of leukocytes downstream of a backward facing step. Here the predicted fluid dynamics in channels incorporating backward facing steps are described, and related to the measured velocities of flowing cells, patterns of attachment and characteristics of rolling adhesion for neutrophils perfused over P‐selectin. Deeper (upstream depth 300 μm, downstream depth 600 μm, maximum wall shear stress ∼0.1 Pa) and shallower (upstream depth 260 μm, downstream depth 450 μm, maximum wall shear stress ∼0.3 Pa) channels were compared. Computational fluid dynamics (CFD) predicted the presence of vortices downstream of the steps, distances to reattachment of flow, local wall shear stresses and components of velocity parallel and perpendicular to the wall. Measurements of velocities of perfused neutrophils agreed well with predictions, and suggested that adhesion to P‐selectin should be possible in the regions of recirculating flow, but not downstream in re‐established flow in the high shear channel. When channels were coated with a P‐selectin–Fc chimaera, neutrophils were captured from flow and immobilised. Capture showed local maxima around the reattachment points, but was absent elsewhere in the high shear chamber. In the low shear chamber there was depression of adhesion just beyond the reattachment point because of expansion of flow and depeletion of neutrophils near the wall. Inside the recirculation zones, adhesion decreased approaching the step because of an increasing, vertically upward velocity component. When channels were coated with P‐selectin, neutrophils rolled in all regions, but lifted off the surface as they rolled backwards into low shear regions near the step. Rolling velocity in the recirculation zone was independent of shear stress, possibly because of the effects of vertical lift. We conclude that while local wall shear stress influences adhesive behavior, delivery of cells to the wall and their behavior after capture also depend on components of flow perpendicular to the wall.
From biomechanics to mechanobiology
Authors: Stoltz J.‐F. , Wang X.
Published: November 2024

Biomechanics can be defined as the application of mechanical concepts to the living world, and various fields of research have been developed such as the mechanics of movement, ergonomics, the mechanical properties of cells and tissues, and the relationship between physiology and applied forces. In this paper, the authors give, through several examples, an outline of these approaches and their potential biomedical applications, as in tissue remodelling, cell and tissue engineering and the development of biotissues.
Human chondrocyte senescence and osteoarthritis
Authors: Martin James A. , Buckwalter Joseph A.
Published: November 2024

Although osteoarthritis (OA) is not an inevitable consequence of aging, a strong association exists between age and increasing incidence of OA. We hypothesized that this association is due to in vivo articular cartilage chondrocyte senescence which causes an age‐related decline in the ability of the cells to maintain articular cartilage, that is, increasing age increases the risk of OA because chondrocytes lose their ability to replace their extracellular matrix. To test this hypothesis, we measured senescence markers in human articular cartilage chondrocytes from 27 donors ranging in age from one to 87 years. The markers included expression of the senescence‐associated enzyme β‐galactosidase, mitotic activity measured by 3H‐thymidine incorporation, and telomere length. β‐galactosidase expression increased with age (r=0.84, p=0.0001) while mitotic activity and mean telomere length declined (r=−0.774, p=0.001 and r=−0.71, p=0.0004, respectively). Decreasing telomere length was strongly correlated with increasing expression of β‐galactosidase and decreasing mitotic activity. These findings help explain the previously reported age related declines in chondrocyte synthetic activity and responsiveness to anabolic growth factors and indicate that in vivo articular cartilage chondrocyte senescence is responsible, at least in part, for the age related increased incidence of OA. The data also imply that people vary in their risk of developing OA because of differences in onset of chondrocyte senescence; and, the success of chondrocyte transplantation procedures performed to restore damaged articular surfaces in older patients could be limited by the inability of older chondrocytes to form new cartilage. New efforts to prevent the development or progression of OA might include strategies that delay the onset of chondrocyte senescence or replace senescent cells.
COX‐1, COX‐2 and articular joint disease: A role for chondroprotective agents
Authors: Colville‐Nash Paul R. , Willoughby Derek A.
Published: November 2024

It is widely accepted that whilst exhibiting clinically useful anti‐inflammatory and analgesic activity, the application of non‐steroidal anti‐inflammatory drugs (NSAIDs) does not affect the underlying pathogenesis of articular diseases such as rheumatoid arthritis. The demonstration of a role for COX‐2 in the resolution of inflammation may partly underly the lack of disease modifying activity seen with NSAIDs in long term use in these inflammatory joint diseases. This has led to the suggestion that the anti‐arthritic efficacy of these agents may be improved by altering prescribing practice such that they are not given during periods of disease remission, which may be difficult to achieve in the clinic. Alternatively, they may benefit from concomitant administration of chondroprotective agents, such as diacetylrhein, which may protect against the deleterious effects of traditional NSAIDs on cartilage degradation and, further, inhibit additional pathways such as cytokine elaboration which are important in joint destruction.
Mechanisms of blood flow‐induced vascular enlargement
Authors: Lehoux Stéphanie , Tronc François , Tedgui Alain
Published: November 2024

Chronic changes in wall shear stress lead to vascular remodeling, characterized by increased vascular wall diameter and thickness, to restore wall shear stress values to baseline. Release of nitric oxide from endothelial cells exposed to excessive shear is a fundamental step in the remodeling process, and potentially triggers a cascade of events, including growth factor induction and matrix metalloproteinase activation, that together contribute to restructuralization of the vessel wall. Understanding these processes could help explain how changes in blood vessel wall structure occur in the context of atherosclerosis or aortic aneurisms.
Unsteady near wall residence times and shear exposure in model distal arterial bypass grafts
Authors: Sherwin S.J. , Doorly D.J. , Franke P. , Peiró J.
Published: November 2024

Building on previous studies of unsteady flow within model distal bypass grafts we analyse the near wall residence times and shear exposure in a 45 degrees anastomosis under symmetrical and symmetry breaking geometric configurations. We define residence time as the minimum time for a particle to exit a spherical region and shear exposure as a temporal integral of the Huber‐Henky‐von‐Mises criterion along a particle path over a fixed time interval. Decomposing the pulsatile cycle into four equal intervals we find that the interval of peak residence time in the host vessel is from mid‐deceleration to peak diastole and peak diastole to mid‐acceleration. The asymmetric model is shown to have a significantly lower residence time during these intervals. Considering the shear exposure prior to the residence time evaluation we determine that a higher average shear exposure exists in the asymmetric model associated with the upstream geometry modification. Analysis of the regions of high residence time and shear exposure suggests that the “toe” region and the interface between the “heel” and bulk flow are more significant than the bed and heel region. Although the asymmetric model considered in this study reduces residence times in the host artery, the product of the measure of shear exposure and residence time is not found to be preferable. If shear exposure were to be considered as an important factor in particle activation, the findings imply that for junction optimisation, greater consideration needs to be given both to the local junction asymmetry and upstream influence on the shear history.
The morphometry and biomechanical properties of the rat small intestine after systemic treatment with epidermal growth factor
Authors: Zhao Jingbo , Yang Jian , Vinter‐Jensen Lars , Zhuang Fengyuan , Gregersen Hans
Published: November 2024

Morphometric and passive biomechanical properties were studied in isolated segments of the duodenum, jejunum and ileum in 22 EGF‐treated rats and 12 control rats. The rats were allocated to groups with EGF treatment for 2, 4, 7, and 14 days (n=6 for each EGF treatment group except n=4 for the 14 days group) or saline treatment (n=3 for each group). The intestinal segments were pressurized with Krebs solution from 0 to 8 cmH2O for duodenum and 0 to 6 cmH2O for jejunum and ileum using a ramp distension protocol. The diameter and length were recorded at different pressure levels. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter, pressure and the zero‐stress state data. EGF treatment was associated with pronounced morphometric changes, e.g., the wall thickness, wall area, and the circumferential lengths significantly increased during EGF treatment in all intestinal segments (P<0.05). Histological analysis showed that the thickness and area of the layers increased after EGF treatment. With respect to the biomechanical data, the opening angle increased in all segments during EGF treatment with the highest value in the 14 days EGF treatment group (P<0.05). The same result was found for residual strain and the residual strain gradient through the intestinal wall. Linear regression analysis demonstrated that the opening angle mainly depended on the mucosa thickness and area. Furthermore, the circumferential stiffness increased in the duodenum and decreased in the jejunum and ileum during EGF treatment. A plateau was reached after 7 days where after it started to normalize (P<0.01). In the longitudinal direction, all intestinal segments became stiffer after EGF treatment for 7 days. After 14 days the curve started to normalize in duodenum and jejunum but not in the ileum.
Upregulation of aggrecan and type II collagen mRNA expression in bovine chondrocytes by the application of hydrostatic pressure
Authors: Toyoda Takashi , Seedhom Bahaa B. , Kirkham Jennifer , Bonass William A.
Published: November 2024

The aim of this study was to investigate the effect of hydrostatic pressure on the expression of messenger ribonucleic acid (mRNA) for specific extracellular matrix proteins in chondrocytes. Chondrocytes obtained from bovine metatarsophalangeal joints were embedded in cylindrical 2% agarose gels. A novel experimental system was used to apply 5 MPa of static hydrostatic pressure to these chondrocytes for 4 hours. The application of hydrostatic pressure caused a significant increase in the level of aggrecan mRNA by almost four fold (p<0.01) as well as a 50% increase in the level of type II collagen mRNA (p<0.05). However, there was no significant change in the level of TIMP‐1 mRNA. It was suggested that the application of hydrostatic pressure, in the absence of cell deformation, can bring about changes in the matrix components which may play an important role in the homeostasis and mechanical properties of articular cartilage.
Comparison of wide‐field/deconvolution and confocal microscopy in bioengineering. Interest of multi‐photon microscopy in the study of articular cartilage
Authors: Dumas D. , Grossin L. , Cauchois G. , Gentils M. , Santus R. , Stoltz J.F.
Published: November 2024

The increase in lateral and spatial resolutions is one of the major targets of research and development in the field of optical microscopies applied to living tissue. The optical geometry of Confocal Laser Scanning Microscopy (CLSM) demonstrates its undeniable advantage on conventional fluorescence microscopy by segregating the planes outside the focussing plane. The methodological and technological advances of the last five years have been fast evolving, especially with regard to the optimisation of CLSM and deconvolution process. The limited analysis in thick tissue have given rise to the development of other techniques, multi‐photon excitation microscopy in particular.

In this paper, we have applied these techniques on major biological applications in bioengineering (endothelial cell, chondrocyte in 3D‐culture, human cartilage) and discussed the technical limitations and perspectives.
Development and validation of a bioreactor for physical stimulation of engineered cartilage
Authors: Démarteau O. , Jakob M. , Schäfer D. , Heberer M. , Martin I.
Published: November 2024

A bioreactor has been developed to apply different regimes of physical stimulation to tissue specimens under highly controlled conditions. The computer‐controlled device exposes specimens to compressive deformation at various strains and frequencies, measures the load applied to each sample and allows simultaneous medium stirring at different velocities. Validation tests confirmed the accuracy of the system in (i) its displacement (errors averaged 0.072±0.051 μm), and in (ii) setting the contact with the samples utilizing micrometer screws coupled to plungers (errors averaged 1.74±0.36% for samples of 1.60–3.18 mm thickness), thus ensuring accurate compressive deformation. The developed bioreactor, which represents an advance in the technology for physical stimulation of tissue specimens, is currently used to apply compressive deformation and hydrodynamic forces to human chondrocytes cultured in biodegradable polymer scaffolds, with the goals of (i) engineering functional grafts for the repair of cartilage defects (ii).
The influence of exercise on bone morphogenic enzyme activity of immature equine subchondral bone
Authors: van de Lest Chris H.A. , Brama Pieter A.J. , van Weeren P.R.
Published: November 2024

This study aimed at the determination of the influence of exercise on the levels of a number of bone morphogenic enzymes in subchondral bone and at the comparison of these data with other (subchondral) bone‐related parameters that have been investigated in the same experimental population.

Forty‐three foals were reared until weaning at 5 months of age under similar conditions, except for the type and amount of exercise. Fifteen foals remained at pasture (Pasture group and also control group), 14 foals were kept in box stalls (Box group) and 14 foals were kept in the same box stalls but were subjected daily to an increasing number of gallop sprints (Training group). After weaning 8 foals from each group were euthanised. All remaining 19 animals were housed together in a loose box with access to a small paddock to study a possible reversibility of exercise‐induced effects. Post mortem subchondral bone samples were collected from the femoropatellar joint and analysed for the bone morphogenic enzymes alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP) and lysyl oxidase (LO). Data were compared to calcium content, numbers of collagen cross‐links, bone mineral density (BMD) and cross‐sectional area (CSA) collected in other bone‐related studies in the same group of experimental animals.

At 5 months of age, ALP levels were significantly lower and TRAP levels higher in both the Box and the Training group, making the ALP : TRAP ratio reversed in relation to the Pasture group. LO levels were lower in the Box group only. The ALP and TRAP data corresponded with changes in CSA, but not with calcium and BMD, the levels of which were the same in the Training and Pasture groups. The LO levels corresponded nicely with hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross‐links. At 11 months of age ALP and TRAP levels had reached similar levels in most groups, normalising the ALP : TRAP ratio. TRAP levels in the former Training group lagged somewhat behind. LO levels were still significantly lower in the former Box rest group.

It is concluded that the overall increase in bone mass (characterised by the change in CSA) is apparently related to continuous, evenly distributed exercise as in the Pasture group (natural situation). This process seems to be related with ALP and TRAP levels and their ratio. For normal cross‐link levels and BMD, short heavy bouts of exercise superimposed on a basic rest regimen seem sufficient. However, both data from this study and from earlier studies suggest that this latter exercise regimen might have a long‐term deleterious effect.
Radial artery wall shear stress evaluation in patients with arteriovenous fistula for hemodialysis access
Authors: Remuzzi Andrea , Ene‐Iordache Bogdan , Mosconi Lidia , Bruno Simona , Anghileri Abramo , Antiga Luca , Remuzzi Giuseppe
Published: November 2024

It has been extensively documented that changes in blood flow induce vascular remodeling and this phenomenon seems to be correlated to the shear forces imposed on the vessel wall by motion of blood. Wall shear stress, the tractive force that acts on the endothelium, has been shown to influence endothelial cell function. To study changes in wall shear stress that develop on the vessel wall upon changes of blood flow, we set up a technique that allows estimation of shear stress in the radial artery of patients on chronic hemodialysis therapy. The technique is based on color‐flow Doppler examination of the radial artery before and after surgical creation of radiocephalic fistula for hemodialysis. Calculation of time function wall shear stress and blood flow rate in the radial artery is performed on the basis of arterial diameter, center‐line velocity waveform and blood viscosity, using a numerical method developed according to Womersley's theory for pulsatile flow in tubes. The results presented confirm that the model developed is suitable for calculation of the wall shear stress that develops in the radial artery of patients before and after surgical creation of an arteriovenous fistula for hemodialysis. This methodology was developed for characterization of wall shear stress in the radial artery but may be well applied to other vessels that can be examined by echo‐Doppler technique.
Inhibition of adhesion of hepatocellular carcinoma cells to basement membrane components by receptor competition with RGD‐ or YIGSR‐containing synthetic peptides
Authors: Wu Ze‐Zhi , Li Ping , Huang Qi‐Ping , Qin Jian , Xiao Guo‐Hui , Cai Shao‐Xi
Published: November 2024

A micropipette technique was used to investigate the effects of four synthetic peptides, YIGSR, CDPGYIGSR, RGDS and GRGDTP, on the adhesion of hepatocellular carcinoma (HCC) cells onto type IV collagen/laminin/fibronectin coated surfaces. Adhesion of HCC cells to laminin was found to be YIGSR‐ or CDPGYIGSR‐dependent while that to fibronectin and type IV collagen was RGDS‐ or GRGDTP‐dependent. The reduction in adhesion strengths of HCC cells was slight to moderate (up to 55%), and was dependent on the peptide concentration. The decrease in adhesion strengths was reversed by an increase in ligand coating concentration and was compromised by prolonged interaction of the cells with the surfaces. These results suggested that the inhibition was due to competitive retardation rather than to a blockade of adhesion strengthening. A simple asymptotic function was adopted to fit the correlation between the mean of cell adhesion strengths and peptide concentration within defined concentration ranges. Regression analysis showed that cell adhesion strengths appeared to approach a plateau with increasing concentration of the inhibitory peptides, which was not always uniform over the entire concentration range tested. Further reduction in adhesion strengths was observed at higher peptide concentrations. It is suggested that the constants obtained by fitting over a low peptide concentration range might be kinetically representative of the inhibition during early events of adhesion or attachment.
Viscoelastic deformation response of red blood cells under conditions of oscillating centrifugal field
Authors: Farges E. , Grebe R. , Baumann M.
Published: November 2024

The red cell deformation under the conditions of oscillating centrifugal fields was studied. Experiments were carried out with a modified Cell‐Elastometer operating in oscillating mode (0.02 to 0.30 Hz). Gravitational acceleration was sinusoidally modulated between 620g and 2250g. At low frequencies (below 0.08 Hz), native red cells followed the applied stress without delay. At 0.09 Hz and up, the cellular deformation was still periodical and included an additional perturbation due to intracellular movements. This perturbation was analysed and quantified. The influence of alterations on the erythrocyte membrane by diamide was analysed to verify the sensitivity of this method. On increasing the membrane stiffness with low concentrations of diamide, the response to oscillatory centrifugal stress was impaired characteristically in terms of amplitude deformation. Based on tangential and centrifugal accelerations, a physical model was developed that describes the basic observable changes on varying the oscillation frequency. From the data it can be concluded that viscoelastic properties of red cells can be analysed and quantified using oscillatory centrifugal accelerations. The described method can become a valid tool to differentiate between membrane alterations or intracellular viscous modifications.
Conductometric study of shear‐dependent processes in red cell suspensions. I. Effect of red blood cell aggregate morphology on blood conductance
Authors: Pribush A. , Meyerstein D. , Meyerstein N.
Published: November 2024

The conductance and capacitance of flowing and quiescent red blood cell (RBC) suspensions were measured at a frequency of 0.2 MHz. The results demonstrate that the time‐dependent changes in the conductance recorded during the aggregation process differ in nature for suspensions of short linear rouleaux, branched aggregates and RBC networks. It is shown that the conductance of RBC suspensions measured during the aggregation and disaggregation processes follows the morphological transformations of the RBC aggregates. Thus, this method enables characterization of the morphology of RBC aggregates formed in whole blood and in suspensions with physiological hematocrits both under flow conditions and in stasis. These results in combination with previous ones suggest that this technique can be used for studies of dynamic RBC aggregation and probably for diagnostic use.
Blood soluble drag‐reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments
Authors: Kameneva Marina V. , Wu Zhongjun J. , Uraysh Arkady , Repko Brandon , Litwak Kenneth N. , Billiar Timothy R. , Fink Mitchell P. , Simmons Richard L. , Griffith Bartley P. , Borovetz Harvey S.
Published: November 2024

Over the past several decades, blood‐soluble drag reducing polymers (DRPs) have been shown to significantly enhance hemodynamics in various animal models when added to blood at nanomolar concentrations. In the present study, the effects of the DRPs on blood circulation were tested in anesthetized rats exposed to acute hemorrhagic shock. The animals were acutely resuscitated either with a 2.5% dextran solution (Control) or using the same solution containing 0.0005% or 5 parts per million (ppm) concentration of one of two blood soluble DRPs: high molecular weight (MW=3500 kDa) polyethylene glycol (PEG‐3500) or a DRP extracted from Aloe vera (AVP). An additional group of animals was resuscitated with 0.0075% (75 ppm) polyethylene glycol of molecular weight of 200 kDa (PEG‐200), which possesses no drag‐reducing ability. All of the animals were observed for two hours following the initiation of fluid resuscitation or until they expired. We found that infusion of the DRP solutions significantly improved tissue perfusion, tissue oxygenation, and two‐hour survival rate, the latter from 19% (Control) and 14% (PEG‐200) to 100% (AVP) and 100% (PEG‐3500). Furthermore, the Control and PEG‐200 animals that survived required three times more fluid to maintain their blood pressure than the AVP and PEG‐3500 animals. Several hypotheses regarding the mechanisms underlying these observed beneficial hemodynamic effects of DRPs are discussed. Our findings suggest that the drag‐reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders.
Magnetizable needles and wires – modeling an efficient way to target magnetic microspheres in vivo
Authors: Iacob Gh. , Rotariu O. , Strachan N.J.C. , Häfeli U.O.
Published: November 2024

The in vivo targeting of tumors with magnetic microspheres is currently realized through the application of external non‐uniform magnetic fields generated by rare‐earth permanent magnets or electromagnets. Our theoretical work suggests a feasible procedure for local delivery of magnetic nano‐ and microparticles to a target area. In particular, thin magnetizable wires placed throughout or close to the target area and magnetized by a perpendicular external uniform background magnetic field are used to concentrate magnetic microspheres injected into the target organ's natural blood supply. The capture of the magnetic particles and the building of deposits thereof in the blood vessels of the target area were modeled under circumstances similar to the in vivo situation. This technique could be applied to magnetically targeted cancer therapy or magnetic embolization therapy with magnetic particles that contain anticancer agents, such as chemotherapeutic drugs or therapeutic radioisotopes.
An automated tube‐type blood viscometer: Validation studies
Authors: Alexy T. , Wenby R.B. , Pais E. , Goldstein L.J. , Hogenauer W. , Meiselman H.J.
Published: November 2024

The technical complexity of previous rheometers has tended to limit the availability of blood viscosity data obtained over a wide range of shear rates. However, an automated tube‐type viscometer, the Rheolog™, has been developed; it employs a disposable flow assembly and less than five minutes are required to obtain blood viscosity results over a shear rate range of 1–1500 s−1. We have carried out validation studies of the Rheolog™ using normal human blood and have compared these results with those obtained by cone‐plate and Couette viscometers; storage time and temperature effects were also evaluated. Replicate measurements indicated mean CV levels less than 5%, and were independent of hematocrit and shear rate. Rheolog™ blood viscosity data agreed closely with those from other viscometers: average Rheolog™ differences from mean cone‐plate and Couette values were −0.3% at 28% hematocrit, −1.4% at 41% hematocrit (i.e., native), and 1.0% at 56% hematocrit. Storage at room temperature up to 8 hours and at 4°C up to 4 days had minimal effects whereas notable changes were observed when stored for 3 hours at 37°C. Our results indicate that, within the hematocrit and shear rate limits employed herein, the Rheolog™ provides rapid, accurate and reproducible blood viscosity data, and suggest its usefulness for both basic science and clinical studies.
Catch bonds: Physical models, structural bases, biological function and rheological relevance
Authors: Zhu Cheng , Lou Jizhong , McEver Rodger P.
Published: November 2024

Force can shorten the lifetimes of macromolecular complexes (e.g., receptor–ligand bonds) by accelerating their dissociation. Perhaps paradoxical at first glance, bond lifetimes can also be prolonged by force. This counterintuitive behavior was named catch bonds, which is in contrast to the ordinary slip bonds that describe the intuitive behavior of lifetimes being shortened by force. Fifteen years after their theoretical proposal, catch bonds have finally been observed. In this article we review recently published data that have demonstrated catch bonds in the selectin system and suggested catch bonds in other systems, the theoretical models for their explanations, possible structural bases, their relation to flow-enhanced adhesion, and the potential biorheological relevance.
Contraction of collagen gels seeded with tendon cells
Authors: Chen M.-Y. , Jeng L. , Sun Y.-L. , Zhao C.-F. , Zobitz M.E. , Moran S.L. , Amadio P.C. , An K.-N.
Published: November 2024

Knowledge of the adaptation of the soft tissue to mechanical factors and biomolecules would be essential to better understand the mechanism of tendon injury and to improve the outcome of tendon repair. The responses to these factors could be different for the distinct types of cells in the tendon: cells from the tendon sheath, fibroblasts from the epitenon surface, or fibroblasts from the internal endotenon. In this study, we examined the mechanical and histological characteristics of the rate of contraction of the collagen gel seeded with epitenon and endotenon fibroblasts. The rate of contraction and the mechanical property of the contracted construct depend on the gel concentration and also the treatment of TGF-β1.
Human chondrocytes and mesenchymal stem cells grown onto engineered scaffold
Authors: Facchini Andrea , Lisignoli Gina , Cristino Sandra , Roseti Livia , De Franceschi Luciana , Marconi Emanuele , Grigolo Brunella
Published: November 2024

The development of improved methods for treatment of chondral defects using autologous cells in combination with biomaterials leads to a new generation of implantable devices. Their association gives rise to a hybrid construct combining biological and material components that can be specifically committed. The comprehension of cellular and molecular mechanisms of cartilage repair and the use of biomaterials in combination with chondrocytes or mesenchymal stem cells in the treatment of cartilage defects has opened a new era of therapeutical strategies. Recently, their applicability in the treatment of early lesions in osteoarthritis is under investigation. To obtain new information on the behaviour of chondrocytes and mesenchymal stem cells grown on a hyaluronan derivative scaffold (Hyaff®-11) already used in cartilage repair, we analysed a series of molecules expressed by these cells by Real-Time RT-PCR and immunohistochemical analyses. The data obtained with this work showed that this biomaterial is able to reduce the expression of some catabolic molecules by human chondrocytes and provide a good environment to support the differentiation of mesenchymal stem cells in chondrogenic sense. These observations confirm Hyaff®-11 as a suitable scaffold both for chondrocytes and mesenchymal stem cells for the treatment of articular cartilage defects.
Bi-zonal cartilaginous tissues engineered in a rotary cell culture system
Authors: Marsano A. , Wendt D. , Quinn T.M. , Sims T.J. , Farhadi J. , Jakob M. , Heberer M. , Martin I.
Published: November 2024

In this study, we aimed at validating a rotary cell culture system (RCCS) bioreactor with medium recirculation and external oxygenation, for cartilage tissue engineering. Primary bovine and human culture-expanded chondrocytes were seeded into non-woven meshes of esterified hyaluronan (HYAFF®-11), and the resulting constructs were cultured statically or in the RCCS, in the presence of insulin and TGFβ3, for up to 4 weeks. Culture in the RCCS did not induce significant differences in the contents of glycosaminoglycans (GAG) and collagen deposited, but markedly affected their distribution. In contrast to statically grown tissues, engineered cartilage cultured in the RCCS had a bi-zonal structure, consisting of an outgrowing fibrous capsule deficient in GAG and rich in collagen, and an inner region more positively stained for GAG. Structurally, trends were similar using primary bovine or expanded human chondrocytes, although the human cells deposited inferior amounts of matrix. The use of the presented RCCS, in conjunction with the described medium composition, has the potential to generate bi-zonal tissues with features qualitatively resembling the native meniscus.
Modeling pulsatile flow in aortic aneurysms: Effect of non-Newtonian properties of blood
Authors: Khanafer Khalil M. , Gadhoke Prateek , Berguer Ramon , Bull Joseph L.
Published: November 2024

Pulsatile flow in an axisymmetric rigid-walled model of an abdominal aorta aneurysm was analyzed numerically for various aneurysm dilations using physiologically realistic resting waveform at time-averaged Reynolds number of 300 and peak Reynolds number of 1607. Discretization of the governing equations was achieved using a finite element scheme based on the Galerkin method of weighted residuals. Comparisons with previously published work on the basis of special cases were performed and found to be in excellent agreement. Our findings indicate that the velocity fields are significantly affected by non-Newtonian properties in pathologically altered configurations. Non-Newtonian fluid shear stress is found to be greater than Newtonian fluid shear stress during peak systole. Further, the maximum shear stress is found to occur near the distal end of AAA during peak systole. The impact of non-Newtonian blood flow characteristics on pressure compared to Newtonian model is found insignificant under resting conditions. Viscous and inertial forces associated with blood flow are responsible for the changes in the wall that result in thrombus deposition and dilation while rupture of AAA is more likely determined by much larger mechanical stresses imposed by pulsatile pressure on the wall of AAA.
Microscopic investigation of erythrocyte deformation dynamics
Authors: Zhao Rui , Antaki James F. , Naik Tikeswar , Bachman Timothy N. , Kameneva Marina V. , Wu Zhongjun J.
Published: November 2024

The understanding of erythrocyte deformation under conditions of high shear stress and short exposure time is central to the study of hemorheology and hemolysis within prosthetic blood contacting devices. A combined computational and experimental microscopic study was conducted to investigate the erythrocyte deformation and its relation to transient stress fields. A microfluidic channel system with small channels fabricated using polydimethylsiloxane on the order of 100 μm was designed to generate transient stress fields through which the erythrocytes were forced to flow. The shear stress fields were analyzed by three-dimensional computational fluid dynamics. Microscopic images of deforming erythrocytes were experimentally recorded to obtain the changes in cell morphology over a wide range of fluid dynamic stresses. The erythrocyte elongation index (EI) increased from 0 to 0.54 with increasing shear stress up to 123 Pa. In this shear stress range, erythrocytes behaved like fluid droplets, and deformed and flowed following the surrounding fluid. Cells exposed to shear stress beyond 123 Pa (up to 5170 Pa) did not exhibit additional elongation beyond EI=0.54. Two-stage deformation of erythrocytes in response to shear stress was observed: an initial linear elongation with increasing shear stress and a plateau beyond a critical shear stress.