Ritman, Erik L.

Owing to recent progress in analytical techniques, metallomics are evolving from detecting distinct trace metals in a defined state to monitor the dynamic changes in the abundance and location of trace metals in vitro and in vivo. Vascular metallomics is an emerging field that studies the role of trace metals in vasculature. This review will introduce common metallomics techniques including atomic absorption spectrometry, inductively coupled plasma-atomic emission spectrometry, inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry with a summary table to compare these techniques. Moreover, we will summarize recent research findings that have applied these techniques to human population studies in cardiovascular diseases, with a particular emphasis on the role of copper in these diseases. In order to address the issue of interdisciplinary studies between metallomics and vascular biology, we will review the progress of efforts to understand the role of copper in neovascularization. This recent advance in the metallomics field may be a powerful tool to elucidate the signaling pathways and specific biological functions of these trace metals. Finally, we summarize the evidence to support the notion that copper is a dynamic signaling molecule. As a future direction, vascular metallomics studies may lead to the identification of targets for diagnosis and therapy in cardiovascular disease.

The constitutive equation with stress-dependent coefficients for laminated composite is derived and employed for iterative determination of myocardial fiber’s stiffness equation Ef = Kσf + C from myocardial strip’s stiffness equation Es = Ksσs + Cs. The strip’s stiffness constants Ks and Cs are estimated by the least-square curve fitting of the stress-strain data experimentally obtained from uniaxially stretching of strips of left ventricular heart wall excised from seven canine hearts. The values of K and C computed at selected fiber orientations across the thickness of the strip and using three, five, and ten-layer approximations are reported.

The objective of this study was to investigate the influence of pore geometry on the transport rate and depth after repetitive mechanical deformation of porous scaffolds for tissue engineering applications. Flexible cubic imaging phantoms with pores in the shape of a circular cylinder, elliptic cylinder, and spheroid were fabricated from a biodegradable polymer blend using a combined 3D printing and injection molding technique. The specimens were immersed in fluid and loaded with a solution of a radiopaque solute. The solute distribution was quantified by recording 20 μm pixel-resolution images in an X-ray microimaging scanner at selected time points after intervals of dynamic straining with a mean strain of 8.6 ± 1.6% at 1.0 Hz. The results show that application of cyclic strain significantly increases the rate and depth of solute transport, as compared to diffusive transport alone, for all pore shapes. In addition, pore shape, pore size, and the orientation of the pore cross-sectional asymmetry with respect to the direction of strain greatly influence solute transport. Thus, pore geometry can be tailored to increase transport rates and depths in cyclically deformed scaffolds, which is of utmost importance when thick, metabolically functional tissues are to be engineered.

The universally accepted concept of delay-loaded dental implants has recently been challenged. This study hypothesizes that early loading (decreased implant healing time) leads to increased bone formation and decreased crestal bone loss. We used 17 minipigs to study implants under a controlled load, with non-loaded implants for comparison. Radiographic and histological assessments were made of the osseointegrated bone changes for 3 healing times (between implant insertion and loading), following 5 months of loading. The effect of loading on crestal bone loss depended on the healing time. Early loading preserved the most crestal bone. Delayed loading had significantly more crestal bone loss compared with the non-loaded controls (2.4 mm vs. 0.64 mm; P < 0.05). The histological assessment and biomechanical analyses of the healing bone suggested that loading and bioactivities of osteoblasts exert a synergistic effect on osseointegration that is likely to support the hypothesis that early loading produces more favorable osseointegration.

Abstract We examined the time course effects of continuous PTH on cortical bone and mechanical properties. PTH increased cortical bone turnover and induced intracortical porosity with no deleterious effect on bone strength. Withdrawal of PTH increased maximum torque to failure and stiffness with no change in energy absorbed. Introduction: The skeletal response of cortical bone to parathyroid hormone (PTH) is complex and species dependent. Intermittent administration of PTH to rats increases periosteal and endocortical bone formation but has no known effects on intracortical bone turnover. The effects of continuous PTH on cortical bone are not clearly established. Materials and Methods: Eighty-four 6-month-old female Sprague-Dawley rats were divided into three control, six PTH, and two PTH withdrawal (WD) groups. They were subcutaneously implanted with osmotic pumps loaded with vehicle or 40 μg/kg BW/day human PTH(1-34) for 1, 3, 5, 7, 14, and 28 days. After 7 days, PTH was withdrawn from two groups of animals for 7 (7d-PTH/7d-WD) and 21 days (7d-PTH/21d-WD). Histomorphometry was performed on periosteal and endocortical surfaces of the tibial diaphysis in all groups. μCT of tibias and mechanical testing by torsion of femora were performed on 28d-PTH and 7d-PTH/21d-WD animals. Results and Conclusions: Continuous PTH increased periosteal and endocortical bone formation, endocortical osteoclast perimeter, and cortical porosity in a time-dependent manner, but did not change the mechanical properties of the femur, possibly because of addition of new bone onto periosteal and endocortical surfaces. Additionally, withdrawal of PTH restored normal cortical porosity and increased maximum torque to failure and stiffness. We conclude that continuous administration of PTH increased cortical porosity in rats without having a detrimental effect on bone mechanical properties.

Abstract Three-dimensional imaging of the intact lung and its vasculature is essential if the hierarchical and volumetric aspects of its structures and functions are to be quantitated. Although this is possible with clinical multislice helical CT scanners, the spatial resolution does not scale down adequately for small rodents for which cubic voxel dimensions of 50–100 μm are required. Micro-computed tomography (micro-CT) provides the necessary spatial resolution of 3D images of the intact thoracic contents. Micro-CT can provide higher resolution so that basic micro-architectural structures, such as alveoli, can be individually visualized and quantitated. Dynamic events, such as the respiratory and cardiac cycles, can be imaged at multiple time points throughout a representative cycle by coordinating the scan sequence (i.e., gating) to the cycle phase of a sequence of cycles. Fusion of the micro-CT image data with other image data, such as micro-SPECT or histology, can enhance the information content beyond the mainly structural information provided by micro-CT. Conventional attenuation-based X-ray imaging can involve significant X-ray exposures at high spatial resolutions, and this could affect the phenotype (e.g., via interstitial fibrosis) and genotype (e.g., via mutation), so its use in longitudinal studies using micro-CT may be limited in some cases. However, because of recent developments in which the phase shift or refraction of X-rays rather than attenuation is used, the X-ray exposure may be significantly reduced.