The therapeutic effects of anti-oxidant and anti-inflammatory drug quercetin on aspiration-induced lung injury in rats

Aspiration pneumonitis refers to acute chemical lung injury caused by aspiration of sterile gastric contents. The aim of this study was to evaluate the role of quercetin (QC) in acid aspiration-induced lung injury in rats. Twenty-eight female Sprague–Dawley rats were used and divided into the following groups (n = 7): sham (aspirated normal saline, S), hydrochloric acid (aspirated HCl), S plus treatment with QC (S + QC), and HCl plus treatment with QC (HCl + QC). After aspiration, the treatment groups received QC 60 mg/kg/day intraperitoneally once a day for 7 days. As a result of acid aspiration, an increase was observed in the levels of serum clara cell protein-16 (CC-16) and advanced oxidation protein products, whereas there was a decrease in serum thiobarbituric acid-reactive substances, superoxide dismutase (SOD), and catalase levels. There was a significant decrease in peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, and alveolar exudate scores, except in the alveolar histiocytes in the HCl + QC group. The expression of nitric oxide synthase, which increased after aspiration in the HCl group, showed a statistically significant decrease after the QC treatment. After the treatment with QC, an increase in the serum SOD level was observed, whereas a significant decrease was determined in the serum CC-16 level relative to that of the aspiration group (HCl). The antioxidant QC is effective in the treatment of lung injury following acid aspiration and can be used as a serum CC-16 biomarker in predicting the severity of oxidative lung injury.     

Spatial patterning of bone stiffness in the anterior mandibular corpus of Macaca fascicularis: Implications for models of bone adaptation

Elastic modulus of bone from the anterior mandibular corpus was determined via microindentation in a mixed-sex ontogenetic sample (N = 14) of Macaca fascicularis. This investigation focused on the hypothesis that material heterogeneity in the macaque mandibular symphysis—provided an accounting of age and sex variation—is explicable as a means to homogenize strains in this region. Experimental data and theoretical models of masticatory loading indicate that in the absence of material compensation, large strain gradients exist in the anterior mandibular corpus of macaques, particularly between lingual and labial cortical plates owing to the effects of lateral transverse bending. Microindentation data indicate that juvenile macaques possess less stiff bone than their subadult and adult counterparts; however, sex differences in elastic modulus are not apparent. Anisotropy variation is idiosyncratic; that is, there is not a common pattern of variation in stiffness sampled among orthogonal planes across individuals. Similarly, differences in stiffness between lingual and labial cortical plates, as well as differences among alveolar, midcorpus, and basal regions are inconsistently observed. Consequently, we find little evidence in support of the hypothesis that spatial variation in bone stiffness functions to homogenize strains in the anterior corpus; in fact, in some individuals, this spatial variation serves to exacerbate, rather than to minimize, strain gradients. The mechanical benefit of elastic modulus variation in the macaque mandibular symphysis is unclear; this variation may not confer adaptive benefit in terms of structural integrity despite the fact that such variation has discernible functional consequences. Am J Phys Anthropol 156:649–660, 2015. © 2014 Wiley Periodicals, Inc.     

Computed modeling of humeral mid-shaft fracture treated by bundle nailing

Elastic bundle nailing is a method for simple humeral mid-shaft fracture osteosynthesis. The aim of our subsequent numerical simulations was to find out torsional and bending stiffness of an elastic bundle nailed humerus. Parametrical 3D numerical model was developed. The diameter of nails was the varying parameter of 1.8, 2.5, 3 and 4 mm. From our results can be seen that the bending stiffness in bundle nailing technique does not depend on nail diameter. On the contrary the torsional stiffness does highly depend on nail diameter. The dependency of the maximal stress on a nail diameter during bending and torsion of the humerus is non-linear. It can be seen that the higher diameter is used the higher stress occurs. Achieved results allow us for the recommendation of optimal nail diameter for this method, which lies between 2 and 3 mm.     

The effect of resorption cavities on bone stiffness is site dependent

Resorption cavities formed during the bone remodelling cycle change the structure and thus the mechanical properties of trabecular bone. We tested the hypotheses that bone stiffness loss due to resorption cavities depends on anatomical location, and that for identical eroded bone volumes, cavities would cause more stiffness loss than homogeneous erosion. For this purpose, we used beam–shell finite element models. This new approach was validated against voxel-based FE models. We found an excellent agreement for the elastic stiffness behaviour of individual trabeculae in axial compression (R² = 1.00) and in bending (R²>0.98), as well as for entire trabecular bone samples to which resorption cavities were digitally added (R² = 0.96, RMSE = 5.2%). After validation, this new method was used to model discrete cavities, with dimensions taken from a statistical distribution, on a dataset of 120 trabecular bone samples from three anatomical sites (4th lumbar vertebra, femoral head, iliac crest). Resorption cavities led to significant reductions in bone stiffness. The largest stiffness loss was found for samples from the 4th lumbar vertebra, the lowest for femoral head samples. For all anatomical sites, resorption cavities caused significantly more stiffness loss than homogeneous erosion did. This novel technique can be used further to evaluate the impact of resorption cavities, which are known to change in several metabolic bone diseases and due to treatment, on bone competence.     

The combined impact of mechanical factors on the wall stress of the human ascending aorta – a finite elements study

Background

Biomechanical factors influence stress in the aortic wall. The aim of this study was to assess how the diameter and shape of the vessel, blood pressure and longitudinal systolic aortic stretching (SAS) caused by the contraction of the myocardium influence stress in the aortic wall.

Methods

Three computational models of the non-dilated aorta and aneurysms of the ascending aorta and aortic root were created. Then, finite elements analyses were carried out. The models were subjected to blood pressure (120 mmHg and 160 mmHg) and longitudinal systolic aortic stretching (0 mm, 5 mm, 10 mm and 15 mm). The influence of wall elasticity was examined too.

Results

Blood pressure had a smaller impact on the stress than the SAS. An increase in blood pressure from 120 mmHg to 160 mmHg increased the peak wall stress (PWS) on average by 0.1 MPa in all models. A 5 mm SAS caused a 0.1–0.2 MPa increase in PWS in all the models. The increase in PWS caused by a 10 mm and 15 mm SAS was 0.2 MPa and 0.4 MPa in the non-dilated aorta, 0.2–0.3 MPa and 0.3–0.5 MPa in the aneurysm of the ascending aorta, and 0.1–0.2 MPa and 0.2–0.3 MPa in the aortic root aneurysm model, respectively. The loss of elasticity of the aneurysmal wall resulted in an increase of PWS by 0.1–0.2 MPa.

Conclusions

Aortic geometry, wall stiffness, blood pressure and SAS have an impact on PWS. However, SAS had the biggest impact on wall stress. The results of this study may be useful in future patient-specific computational models used to assess the risk of aortic complications.

     

Determination of mechanical stiffness of bone by pQCT measurements: correlation with non-destructive mechanical four-point bending test data

Mechanical tests of bone provide valuable information about material and structural properties important for understanding bone pathology in both clinical and research settings, but no previous studies have produced applicable non-invasive, quantitative estimates of bending stiffness. The goal of this study was to evaluate the effectiveness of using peripheral quantitative computed tomography (pQCT) data to accurately compute the bending stiffness of bone. Normal rabbit humeri (N=8) were scanned at their mid-diaphyses using pQCT. The average bone mineral densities and the cross-sectional moments of inertia were computed from the pQCT cross-sections. Bending stiffness was determined as a function of the elastic modulus of compact bone (based on the local bone mineral density), cross-sectional moment of inertia, and simulated quasistatic strain rate. The actual bending stiffness of the bones was determined using four-point bending tests. Comparison of the bending stiffness estimated from the pQCT data and the mechanical bending stiffness revealed excellent correlation (R2=0.96). The bending stiffness from the pQCT data was on average 103% of that obtained from the four-point bending tests. The results indicate that pQCT data can be used to accurately determine the bending stiffness of normal bone. Possible applications include temporal quantification of fracture healing and risk management of osteoporosis or other bone pathologies.     

DNA force-extension curve under uniaxial stretching

Single-molecule experiments indicate that a double-stranded DNA (ds‐DNA) increases in length if put under tension greater than 10 pN; beyond this point, its conformation can no longer be described using an inextensible worm-like chain model. For this purpose, a general sequence-dependent elastic model for tensions greater than 10 pN and for both single-stranded (ss) and ds‐DNA is proposed, and the effective elastic bending and torsional rigidities are determined from experiments to characterise their deformation. The key to this progress is that the bending and torsional deformations of the DNA backbones, the base-stacking interactions and the hydrogen bond force between the complementary base pairs are quantitatively considered in this model. Moreover, this simple elastic model can be used to globally fit to the abrupt B–S experimental transition data over a wide range of DNA molecule extensions. Based on this robust model, further study may be warranted on the mechanical response of ss- and ds‐DNA molecules.     

Contribution to FE modeling for intraoperative pedicle screw strength prediction

Although the use of pedicle screws is considered safe, mechanical issues still often occur. Commonly reported issues are screw loosening, screw bending and screw fracture. The aim of this study was to develop a Finite Element (FE) model for the study of pedicle screw biomechanics and for the prediction of the intraoperative pullout strength. The model includes both a parameterized screw model and a patient-specific vertebra model. Pullout experiments were performed on 30 human cadaveric vertebrae from ten donors. The experimental force-displacement data served to evaluate the FE model performance. μCT images were taken before and after screw insertion, allowing the creation of an accurate 3D-model and a precise representation of the mechanical properties of the bone. The experimental results revealed a significant positive correlation between bone mineral density (BMD) and pullout strength (Spearman ρ = 0.59, p < 0.001) as well as between BMD and pullout stiffness (Spearman ρ = 0.59, p < 0.001). A high positive correlation was also found between the pullout strength and stiffness (Spearman ρ = 0.84, p < 0.0001). The FE model was able to reproduce the linear part of the experimental force-displacement curve. Moreover, a high positive correlation was found between numerical and experimental pullout stiffness (Pearson ρ = 0.96, p < 0.005) and strength (Pearson ρ = 0.90, p < 0.05). Once fully validated, this model opens the way for a detailed study of pedicle screw biomechanics and for future adjustments of the screw design.     

Neuregulin-ErbB4 signaling in the developing lung alveolus: a brief review

Lung immaturity is the major cause of morbidity and mortality in premature infants, especially those born <28 weeks gestation. Proper lung development from 23–28 weeks requires coordinated cell proliferation and differentiation. Infants born at this age are at high risk for respiratory distress syndrome (RDS), a lung disease characterized by insufficient surfactant production due to immaturity of the alveoli and its constituent cells in the lung. The ErbB4 receptor and its stimulation by neuregulin (NRG) plays a critical role in surfactant synthesis by alveolar type II epithelial cells. In this review, we first provide an introduction to normal human alveolar development, followed by a discussion of the neuregulin and ErbB4-mediated mechanisms regulating alveolar development and surfactant production.     

Validation of composite finite elements efficiently simulating elasticity of trabecular bone

Patient-specific analyses of the mechanical properties of bones become increasingly important for the management of patients with osteoporosis. The potential of composite finite elements (CFEs), a novel FE technique, to assess the apparent stiffness of vertebral trabecular bone is investigated in this study. Segmented volumes of cylindrical specimens of trabecular bone are compared to measured volumes. Elasticity under uniaxial loading conditions is simulated; apparent stiffnesses are compared to experimentally determined values. Computational efficiency is assessed and recommendations for simulation parameters are given. Validating apparent uniaxial stiffnesses results in concordance correlation coefficients 0.69 ≤ r_𝒸 ≤ 0.92 for resolutions finer than 168 μm, and an average error of 5.8% between experimental and numerical results at 24 μm resolution. As an application, the code was used to compute local, macroscopic stiffness tensors for the trabecular structure of a lumbar vertebra. The presented technique allows for computing stiffness using smooth FE meshes at resolutions that are well achievable in peripheral high resolution quantitative CT. Therefore, CFEs could be a valuable tool for the patient-specific assessment of bone stiffness.     

Effects of wall distensibility in hemodynamic simulations of an arteriovenous fistula

Arteriovenous fistulae are created surgically to provide adequate access for dialysis patients suffering from end-stage renal disease. It has long been hypothesized that the rapid blood vessel remodeling occurring after fistula creation is in part a process to restore the mechanical stresses to some preferred level, i.e., mechanical homeostasis. The current study presents fluid–structure interaction (FSI) simulations of a patient-specific model of a mature arteriovenous fistula reconstructed from 3D ultrasound scans. The FSI results are compared with previously published data of the same model but with rigid walls. Ultrasound-derived wall motion measurements are also used to validate the FSI simulations of the wall motion. Very large time-averaged shear stresses, 10–15 Pa, are calculated at the fistula anastomosis in the FSI simulations, values which are much larger than what is typically thought to be the normal homeostatic shear stress in the peripheral vasculature. Although this result is systematically lower by as much as 50 % compared to the analogous rigid-walled simulations, the inclusion of distensible vessel walls in hemodynamic simulations does not reduce the high anastomotic shear stresses to “normal” values. Therefore, rigid-walled analyses may be acceptable for identifying high shear regions of arteriovenous fistulae.     

Interactive graph-cut segmentation for fast creation of finite element models from clinical ct data for hip fracture prediction

In this study, we propose interactive graph cut image segmentation for fast creation of femur finite element (FE) models from clinical computed tomography scans for hip fracture prediction. Using a sample of N = 48 bone scans representing normal, osteopenic and osteoporotic subjects, the proximal femur was segmented using manual (gold standard) and graph cut segmentation. Segmentations were subsequently used to generate FE models to calculate overall stiffness and peak force in a sideways fall simulations. Results show that, comparable FE results can be obtained with the graph cut method, with a reduction from 20 to 2–5 min interaction time. Average differences between segmentation methods of 0.22 mm were not significantly correlated with differences in FE derived stiffness (R² = 0.08, p = 0.05) and weakly correlated to differences in FE derived peak force (R² = 0.16, p = 0.01). We further found that changes in automatically assigned boundary conditions as a consequence of small segmentation differences were significantly correlated with FE derived results. The proposed interactive graph cut segmentation software MITK-GEM is freely available online at https://simtk.org/home/mitk-gem.     

Histomorphological evaluation of maternal and neonatal distal airspaces after maternal intake of nanoparticulate titanium dioxide: an experimental study in Wistar rats

This study was performed to determine the histomorphological alterations occurring in maternal and neonatal pulmonary distal airspaces of Wistar rats after maternal administration of titanium dioxide nanoparticles (TiO₂ NPs). Thirty adult pregnant rats (150–250 g) and their offspring were used in this study. Pregnant rats were randomly divided into control (n = 15) and TiO₂ NP-treated (n = 15) groups. A suspension of TiO₂ NPs in phosphate-buffered saline was given orally to the treated group (0.1 ml/10 g body weight once daily) from days 6 to 12 of gestation. At term, maternal and neonatal lungs were collected and processed for energy-dispersive X-ray (EDX) and histological analysis. The mean linear intercept (MLI) and airspace wall thickness were measured by a stereological procedure with image analysis to assess alveolarization. EDX analysis demonstrated the presence of TiO₂ in maternal and neonatal lungs. The lungs of TiO₂ NP-treated mothers revealed evidence of pneumocytic apoptosis, abnormal lamellar inclusions, and macrophage and inflammatory cell infiltrates. Significant thinning of alveolar septa was detected in the treated rats (p < 0.001), but the MLI was constant in both groups (p = 0.207). Neonatal lungs from treated mothers revealed deficient septation, thickened mesenchyme between the saccules, pneumocytic apoptosis, atypical lamellar inclusions, and macrophage infiltration. The thickness of the primary septa was significantly increased (p = 0.001) with no significant change in MLI (p = 0.579) compared with the control group. In conclusion, TiO₂ NPs were detected in maternal and neonatal lungs after oral intake by pregnant rats. The pulmonary response manifested as inflammatory lesions and delayed saccular development in neonates.     

Minimum Membrane Bending Energies of Fusion Pores

Membranes fuse by forming highly curved intermediates, culminating in structures described as fusion pores. These hourglass-like figures that join two fusing membranes have high bending energies, which can be estimated using continuum elasticity models. Fusion pore bending energies depend strongly on shape, and the present study developed a method for determining the shape that minimizes bending energy. This was first applied to a fusion pore modeled as a single surface and then extended to a more realistic model treating a bilayer as two monolayers. For the two-monolayer model, fusion pores were found to have metastable states with energy minima at particular values of the pore diameter and bilayer separation. Fusion pore energies were relatively insensitive to membrane thickness but highly sensitive to spontaneous curvature and membrane asymmetry. With symmetrical bilayers and monolayer spontaneous curvatures of ?0.1 nm^?1 (a typical value) separated by 6 nm (closest distance determined by repulsive hydration forces), fusion pore formation required 43–65 kT. The pore radius of ~2.25 nm fell within the range estimated from conductance measurements. With bilayer separation >6 nm, fusion pore formation required less energy, suggesting that protein scaffolds can promote fusion by bending membranes toward one another. With nonzero spontaneous monolayer curvature, the shape that minimized the energy change during fusion pore formation differed from the shape that minimized its energy after it formed. Thus, a nascent fusion pore will relax spontaneously to a new shape, consistent with the experimentally observed expansion of nascent fusion pores during viral fusion.     

Failure modelling of trabecular bone using a non-linear combined damage and fracture voxel finite element approach

Trabecular bone tissue failure can be considered as consisting of two stages: damage and fracture; however, most failure analyses of 3D high-resolution trabecular bone samples are confined to damage mechanisms only, that is, without fracture. This study aims to develop a computational model of trabecular bone consisting of an explicit representation of complete failure, incorporating damage criteria, fracture criteria, cohesive forces, asymmetry and large deformation capabilities. Following parameter studies on a test specimen, and experimental testing of bone sample to complete failure, the asymmetric critical tissue damage and fracture strains of ovine vertebral trabecular bone were calibrated and validated to be compression damage ?1.16 %, tension damage 0.69 %, compression fracture ?2.91 % and tension fracture 1.98 %. Ultimate strength and post–ultimate strength softening were captured by the computational model, and the failure of individual struts in bending and shear was also predicted. This modelling approach incorporated a cohesive parameter that provided a facility to calibrate ductile–brittle behaviour of bone tissue in this non-linear geometric and non-linear constitutive property analyses tool. Finally, the full accumulation of tissue damage and tissue fracture has been monitored from range of small magnitude (normal daily loading) through to specimen yielding, ultimate strength and post–ultimate strength softening.     

Propagation Properties of Nanoscale Three-Dimensional Plasmonic Waveguide Based on Hybrid of Two Fundamental Planar Optical Metal Waveguides

In this paper, a nanoscale three-dimensional plasmonic waveguide (TDPW), created by depositing an Ag stripe on a SiO₂ layer with an Ag substrate, is introduced and theoretically investigated at visible and telecom wavelengths. By applying the effective index method and finite-difference time-domain numerical simulations, the authors find that the propagation properties of surface plasmon polaritons (SPPs) in the TDPW, including the propagation length and beam width, are mainly decided by the core (the SiO₂ layer just under the Ag stripe) itself, due to the much stronger localization of SPPs in the core than in the two side claddings (the SiO₂ layer without the covered Ag stripe). And propagating SPPs in the TDPW are strongly confined in the core region, even with a very small waveguide cross section. Furthermore, based on the stronger localization of propagation SPPs in the TDPW, two kinds of bending waveguides, oblique bending and 90° circular bending waveguides, are also investigated. For wavelength of 1550 nm, the 90° circular bending guide with a minimum radius as small as 2.6 μm show nearly zero radiation loss, even with a small waveguide cross section of 70?×?80 nm². The proposed TDPW is suitable for planar integration and provides a possible way for constructing various nanoscale counterparts of conventional integrated devices such as splitter, resonator, sensor, and optical switch.     

Study of the properties of doxorubicin-resistant cells affected by acute leucosis

The stiffness of cell membrane was found to be one of the factors determining resistance of a cell in vitro to antibiotic doxorubicin action. Membranes of surviving cells are negatively charged (?35 – ?30 mV) and have high values of stiffness (2.2–5.1 μРа) at the doxorubicin concentrations in the medium of 1–500 μg/ml. If the drug concentration and exposure time are being increased, only cells with ‘soft’ membrane (0.25–1 μРа) and positive surface potential (15–29 mV) survive. The data obtained have important prognostic value in studying drug resistance of tumour blood cells and can be used as objective markers of efficiency of the antitumor therapy.     

Numerical simulation of airflow and microparticle deposition in a synchrotron micro-CT-based pulmonary acinus model

The acinus consists of complex, branched alveolar ducts and numerous surrounding alveoli, and so in this study, we hypothesized that the particle deposition can be much influenced by the complex acinar geometry, and simulated the airflow and particle deposition (density = 1.0 g/cm³, diameter = 1 and 3 μm) numerically in a pulmonary acinar model based on synchrotron micro-CT of the mammalian lung. We assumed that the fluid–structure interaction was neglected and that alveolar flow was induced by the expansion and contraction of the acinar model with the volume changing sinusoidally with time as the moving boundary conditions. The alveolar flow was dominated by radial flows, and a weak recirculating flow was observed at the proximal side of alveoli during the entire respiratory cycle, despite the maximum Reynolds number at the inlet being 0.029. Under zero gravity, the particle deposition rate after single breathing was less than 0.01, although the particles were transported deeply into the acinus after inspiration. Under a gravitational field, the deposition rate and map were influenced strongly by gravity orientation. In the case of a particle diameter of 1 μm, the rate increased dramatically and mostly non-deposited particles remained in the model, indicating that the rate would increase further after repeated breathing. At a particle diameter of 3 μm, the rate was 1.0 and all particles were deposited during single breathing. Our results show that the particle deposition rate in realistic pulmonary acinar model is higher than in an idealized model.     

BENDING STIFFNESS OF CYLINDRICAL PLANT ORGANS WITH A ‘CORE-RIND’ CONSTRUCTION: EVIDENCE FROM JUNCUS EFFUSUS LEAVES

The mechanical behavior of leaves of Juncus effusus L. in bending was investigated in terms of a closed-form analytical solution derived to predict the bending stiffness of a cylindrical sandwich beam consisting of an outer ‘rind’ (sclerenchyma and chlorenchyma) and an inner ‘core’ (aerenchyma). The elastic moduli (E_TOTAL) of intact leaves was measured by means of multiple resonance frequency spectra and compared to that of leaves for which the aerenchymatous core was surgically destroyed. Based on ten leaves, E_TOTAL = 22.33 × 10⁴ ± 5.37 ± 10⁴ kg · cm^–2 while the elastic modulus of the ‘rind’ was 22.29 × 10⁴ ± 5.69 × 10⁴ kg · cm^–2. The elastic modulus of the ‘core’ was estimated at 3.12 × 10⁴ ± 1.42 × 10⁴ kg · cm^–2. Load-deflection curves for three leaf segments indicated leaves were linearly elastic within the range of loading and could be predicted with considerable accuracy based on the closed-form solution. The aerenchymatous core was found to contribute very little to the bending stiffness of leaves, although its contribution appeared to increase as leaf diameter decreased. Leaves mechanically failed by Brazier buckling when excessively loaded and were best considered to mechanically operate as hollow tubes. Nonetheless, the analytical solution for bending stiffness could be applied and, in theory, can be used to predict the behavior of other plant organs with a ‘corerind’ construction.