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S J Simske

Publications and source records attributed to S J Simske.

At least 37 records · Page 2Linked to original sources

Differing effects of two-week suspension on male and female mouse bone metabolism.

The effects of suspension on bone histomorphometry during the first and second week of tail suspension are compared for male and female mice of the common inbred strain, the C57BL/6J. In male mice, significant changes in bone formation rate (BFR) were largely confined to the endocortical perimeter. BFR along the endocortical mid-diaphysis in the femora of suspended male mice was reduced 54.1% and 55.6% for the first and second week, respectively. In female mice, however, measured metabolic changes due to suspension occurred along the periosteal perimeter, where there was a decrease in BFR of 58.3% for the first week and 60.9% for the second. The notable difference in the bone perimeter affected by suspension observed in male and female mice indicates a difference in the metabolic control of bone development in male and female C57BL/6J mice. More importantly, this may indicate a sex-based difference in preserving structural properties in the response of the skeleton to unloading.

Animals↗

Correlation of flexural structural properties with bone physical properties: a four species survey.

The present investigation explores the relationship between animal and bone physical traits and the mechanical properties of whole bone from four species. Mechanical testing was performed using three-point flexure on the femora and tibiae of mice, rats, rabbits and cats. Interspecies correlations of the physical traits to the mechanical properties were used to elucidate the most likely physical predictors of mechanical properties within a single species. Physical traits measured were total bone length (BL), mid-diaphyseal cortical area (CA), body mass (BM), body mass times bone length (BMBL) and bone dry mass (DM). Bone mechanical parameters determined by flexure testing to failure were the structural properties of stiffness (S), elastic strength (Pe), maximum strength (Pm), and the material properties of modulus of elasticity (E), elastic stress (sigma e), and elastic strain (epsilon e). Linear regressions were used to relate the physical trait to the mechanical properties. Interspecies regressions of physical traits to mechanical characteristics implied bone dry mass (DM) is a significant predictor of bone structural properties. Further evidence of this relationship was obtained by exploring the linear relationship for the femora of a single species (rabbit, N = 17) in which age and bone size were allowed to vary. Strength at the elastic limit (in N) within a single species was described by the equation, Pe = 42.9*DM + 42.9 +/- 42.0N, where DM is in grams.

Animals↗

Suspension osteopenia in mice: whole body electromagnetic field effects.

Whole-body fields were tested for their efficacy in preventing the osteopenia caused by tail suspension in mice. The fields had fundamental frequencies corresponding to the upper range of predicted endogenous impact-generated frequencies (0.25-2.0 kHz) in the long bones. Three distinct whole-body EMFs were applied for 2 weeks on growing mice. Structural, geometric, and material properties of the femora, tibiae, and humeri of suspended mice were altered compared to controls. Comparison of suspended mice and mice subjected to caloric restriction indicates that the changes in caloric intake do not explain either the suspension or the field-induced effects. In agreement with past studies, rather, unloading appears to cause the suspension effects and to be addressed by the EMFs. The EMF effects on bone properties were apparently frequency dependent, with the lower two fundamental frequencies (260 and 910 Hz) altering, albeit slightly, the suspension-induced bone effects. The fields are not apparently optimized for frequency, etc., with respect to therapeutic potential; however, suspension provides a model system for further study of the in vivo effects of EMFs.

Animals↗

Cranial bone apposition and ingrowth in a porous nickel-titanium implant.

A 5 x 5 x 1-mm uncoated porous nickel-titanium (nitinol) implant was placed 4 mm to either side of the midsection of the frontal bone and 4 mm anterior to the coronal suture of the cranial bone of New Zealand White rabbits. In the other frontal location, a 5 x 5 x 1-mm coralline hydroxyapatite (HA) (Interpore 200, a well-known craniofacial implant material) implant was fitted. Rabbits were killed at each of three postsurgical intervals (2, 6, and 12 weeks), and the implants were evaluated for gross biocompatibility, bony contact, and ingrowth. No adjacent macrophage cells were observed for either implant type, and overlaying soft tissues and connective tissues readily adhered to the implants even after 2 weeks. Both materials made bone contact with the surrounding cranial hard tissue, and percent ingrowth increased with surgical recovery time. Measurements of microhardness and bone histologic parameters indicated that bone in contact with and grown into the implants was similar in properties to the surrounding cranial bone. Porous nitinol implants therefore appear to allow for significant cranial bone ingrowth after as few as 12 weeks, and thus nitinol appears to be suitable for craniofacial applications. Compared to HA, the nitinol implants demonstrated a trend for less total apposition and more total ingrowth after 6 and 12 weeks of implantation.

Alloys↗

Material and compositional properties of selectively demineralized cortical bone.

Timed immersion in buffered ethylenediamine-tetraacetic acid (EDTA) was used to selectively alter the mineral content at each level in the cortical bone structural hierarchy. The effects on the mechanical behavior were investigated using a combination of experimental techniques which provide collectively a wide range of resolution (5 microns to 3 mm). Optical microscopy and histological analysis demonstrated a heterogeneous structure consisting of a mineralized tissue core surrounded by a layer of demineralized tissue (collagen) whose thickness varied depending on the immersion time. The mechanical behaviors of treated samples with (intact) and without (core) the surrounding demineralized layer were evaluated using three-point flexure. Overall, the intact specimens became significantly less brittle with increased immersion time in buffered-EDTA. For the core specimens, there was a systematic decrease in the elastic flexural properties (E, sigma e, epsilon e). The site-specific properties of the specimens were determined using microhardness testing, scanning acoustic microscopy, and wavelength dispersive analysis. The mineralization and site-specific properties of the mineralized cores were not significantly affected by buffered-EDTA immersion; however, histomorphometric analysis showed a decrease in the mineralized volume fraction via widening of the pre-existing vascular channels. The experimental hierarchy was effective in discerning site-specific property changes and the localized heterogeneities resulting from the buffered-EDTA treatment. Based on the results of this study, buffered-EDTA treatment can be used to facilitate the determination of material and physical properties of intact and demineralized tissues within a single cortical bone sample.

Animals↗

Bone changes in mucopolysaccharidosis VI in cats and the effects of bone marrow transplantation: mechanical testing of long bones.

Mucopolysaccharidosis VI (MPS VI) is a genetic lysosomal storage disease in which a defect in aryl sulfatase B leads to accumulation of the glycosaminoglycan dermatan sulfate and abnormalities in the development of cartilage and bone. A feline model of this disease was used to evaluate the efficacy of bone marrow transplant (BMT) therapy. Long bones from MPS VI cats (N = 6) and MPS VI + BMT cats (N = 7) were compared with control cats (N = 11) and control + BMT cats (N = 5) in mechanical tests. Dissected femurs and tibias were subjected to three-point bending and a subgroup of tibias were tested with the mechanical response tissue analyzer (MRTA) in which vibration is used to measure tissue impedance. Cats with MPS VI had markedly decreased stiffness and strength in both bone (p < 0.01). There was no significant difference in the MPS VI + BMT group. In the tibias, there was also decreased stiffness and strength in the control + BMT group as compared to controls (p < 0.05). However, when cross-sectional area was used to normalize for bone size there was good correlation with strength in both femurs (r = 0.907, p < 0.01) and tibias (r = 0.915, p < 0.1), and there were no significant differences between groups in the modulus of elasticity. In the tibias, in which stiffness was measured by MRTA, there was significant correlation with three-point bending stiffness. These results indicate that, in cats with MPS VI, the decreases in stiffness and strength of long bones can be largely accounted for by the decrease in bone size (osteopenia) that is present.

Animals↗

Effect of microgravity, temperature, and concentration on fibrin and collagen assembly.

In purified form collagen and fibrin can be processed into gel-like matrices of interconnecting fibers. The microscopic structure of materials produced from these macromolecules is critical to their utility as biomaterials. Varying the conditions of the assembly environment allows for the production of a wide range of morphologies. In this study, changes in gravity, temperature, and concentration were examined. Contrary to protein crystal growth studies which indicate substantial increases in organization and size in microgravity, the gravitational environment had no repeatable effect on collagen and fibrin fiber diameters and matrix porosity. However, fibrin gels formed in microgravity appeared more homogeneous than ground samples. Changes in temperature and concentration of both protein and buffer had substantial effects on fiber diameters and material porosity for both collagen and fibrin. Temperature experiments were performed over the range 23.8 to 39 degrees C for fibrin and 22 to 33 degrees C for collagen. Thrombin concentration was varied from 0.02 to 0.10 units/ml for fibrin experiments and buffer concentration was varied by means of a dialysis membrane for collagen experiments. Consequently, the temperature and concentration controls developed for flight experiments are being considered for their potential in developing fibrin and collagen based materials with well-defined microscopic structures. The increased homogeneity of fibrin gels produced in microgravity suggests the possibility of using this environment for the production of optimal biomaterials.

Animals↗

An autonomous module for supporting mice during spaceflight.

The Animal Module for Autonomous space Support (A-MASS) was developed to enable 30-day spaceflight for mice on the first Commercial Experiment Transporter mission. Because space hardware did not previously exist to support mice without astronaut intervention, the A-MASS presented considerable technical and animal care challenges. The technical challenges included maintaining a 42.5l payload volume and 20-g structural conformance while providing 30 days of autonomous mouse support. Sensors, video, a pressurized oxygen supply system and an internal data logging system were incorporated. The A-MASS met NIH guidelines for temperature, humidity, food and water access, oxygen supply, air quality and odor control. These technical and animal care challenges, along with power and mass constraints, were addressed using a novel design which ensures a fresh food and water supply, a clean view path into the cage for the camera system, and removal of the wastes from the air supply. The payload was successfully tested in an enclosed chamber and passed animal health, vibrational, mechanical, and electrical tests. The physiological, tactical and animal support information gathered will be applicable to the development of mouse support modules for the Shuttle Middeck and Space Station Freedom Express Rack environments.

Animal Welfare↗

Contribution of dietary and loading changes to the effects of suspension on mouse femora.

The present study assessed the contributions of feeding changes and unloading to the overall measured effects of 2-wk hindlimb (Tail) suspension on the mouse femora. Feeding changes were addressed by considering the effects of matched feeding among suspended and control mice. The effects of hind limb unloading were considered by comparing suspended mice to mice equipped identically (though not suspended) and matched-fed. The feeding and unloading aspects of suspension appear to cause distinctly differing effects on the stereotypic modeling of the femora. Matched-feeding was accompanied by increased resorption surface in comparison to suspended mice, while unloading led to reduced bone formation at the mid-diaphysis of the femora. Reduced mineral content was observed in the bones of suspended mice when compared to the other mice groups, but without increased resorption surface. Thus, the unloading aspects of the antiorthostatic suspension protocol apparently causes reduced formation and mineralization in the femur.

Animals↗

Class I and class II major histocompatibility molecules play a role in bone marrow-derived macrophage development.

Class I and class II major histocompatibility complex (MHC) molecules play significant roles in T cell development and immune function. We show that MHCI- and MHCII-deficient mice have low numbers of macrophage precursors and circulating monocytes, as well as abnormal bone marrow cell colony-stimulating factor type 1 secretion and bone composition. We suggest that MHCI and MHCII molecules play a significant role in macrophage development.

Animals↗

Effect of microgravity on collagenase deproteinization and EDTA decalcification of bone fragments.

Undecalcified (n = 140) and decalcified (n = 11) bone fragments were treated with either collagenase (to remove collagen portion; undecalcified n = 64, decalcified n = 11) or EDTA (to remove mineral portion; n = 76) under the reduced gravity environment on US Space Shuttle mission STS-57. The fragments were initially stored in Dulbecco's phosphate buffer solution. After orbit had been established, fragments were exposed to either a neutral buffered collagenase or EDTA solution. Reactions were terminated (neutral buffered formalin for collagenase, 21% CuSO4 5H2O for EDTA) before reentry to earth's atmosphere. Differences in bone samples mass from before flight to after flight were measured. EDTA-treated sample mass was corrected for CuSO4 content. Flight and matched ground (gravitational control) sample showed similar EDTA-induced loss of mineral mass. Collagenase treatments, however, appeared to be more effective in flight samples compared to ground control samples. The flight-exposed, collagenase-treated samples showed significantly more loss of mass than did ground samples. The microgravity environment appeared to promote proteolytic reactions in bone more than the EDTA decalcification reaction.

Animals↗

The role of sex and genotype on antiorthostatic suspension effects on the mouse peripheral skeleton.

Previous antiorthostatic suspension studies have used a single sex and strain of rat or mouse. Nonetheless, broadly similar effects of suspension on the two species indicates a generalized effect of suspension not attributed to specific genetic, behavioral, or sex-linked etiology. In order to directly test genetic and sex-linked factors, the effects of suspension on the appendicular bone of male and female BALB-CJ, C57BL-6J, and DBA-2J mice were compared. These genotypes were selected based on their widely different developmental and behavioral characteristics as well as on past research involving a heterogeneous strain derived from these strains. The effects of suspension on the geometric, mechanical, and material properties of the femora, humeri, and tibiae were determined. Among the bone types, the femora were most significantly affected by suspension. The effects of suspension were similar in nature in male and female mice aged 1.7 months. Strain-dependent suspension effects may be indicative of bone developmental differences in the strains at the age chosen.

Animals↗

Effects of rehydration state on the flexural properties of whole mouse long bones.

The effects of bone water content during dehydration and rehydration on the flexural properties of whole mouse femora were evaluated using three-point bending. The elastic and plastic flexural properties of the bones were determined on a dry mass normalized basis over dehydration times ranging from 0.25 to 48.0 hr; and (following complete dehydration) rehydration times ranging from 0.08 to 12.0 hr. Bones stored in physiological saline for times < 1 hr served as the control group. As expected, dehydration produced increased stiffness and strength along with decreased ductility. Upon rehydration, a statistically significant linear dependence of mechanical properties on recovered free water was obtained for all parameters except the maximum load. Elastic mechanical properties comparable to the controls were regained at differing rates and levels of recovered water content; however, after 3 hr of rehydration there were no statistically significant differences with respect to the control values. The results of this study indicate that the original flexural properties of whole mouse femora are preserved by air dehydration and can be recovered using appropriate saline rehydration intervals.

Animals↗

Skeletal unloading causes organ-specific changes in immune cell responses.

The effects of skeletal unloading using antiorthostatic tail suspension on the mouse immune system are tissue specific. This phenomenon was demonstrated by analyzing cells from the lymph nodes, spleen, and bone marrow. Phytohemagglutinin-induced T-cell proliferation was depressed in lymph nodes after 11 days of antiorthostatic suspension. In contrast, splenic T-cell proliferation in response to phytohemagglutinin was enhanced. Splenic natural killer cell cytotoxicity was unchanged after suspension, which demonstrated the organ- and cell-specific effects of skeletal unloading. Whereas antiorthostatic suspension induced minimal changes in bone, there was a significant depression in the number of macrophage precursors in the bone marrow. Overall, skeletally unloaded animals had slightly higher blood corticosterone levels than did control animals; however, it did not appear to be responsible for the observed changes. In conclusion, skeletal unloading produces organ- and cell-specific changes in the murine immune system rather than a generalized immunosuppression.

Animals↗

The physical and mechanical effects of suspension-induced osteopenia on mouse long bones.

The present investigation addresses the extent of tail-suspension effects on the long bones of mice. The effects are explored in both sexes, in both forelimb and hindlimb bones, and in both diaphyseal and metaphyseal/epiphyseal bones. Two weeks of suspension provided unloading of the femora and tibiae and an altered loading of the humeri. Whole-bone effects included lower mass (approximately 10%) and length (approximately 4%) in the bones of suspended mice compared to controls. The geometric and material properties of the femora were considered along the entire length of the diaphysis and in the metaphysis/epiphysis portions as a unit. Geometric effects included lower cross-sectional cortical area (16%), cortical thickness (25%) and moment of inertia (21%) in the femora of suspended mice; these differences were observed in both distal and proximal portions of the femur diaphysis. The relative amount of bone comprising the middle 8 mm of the diaphysis was greater (3%) in the control mice than in the suspended mice. Significant mass differences between the group in the metaphysis/epiphysis were not observed. Material effects included lower %ash (approximately 2%) in the femora and tibiae as well as in the humeri of suspended mice compared to controls. With respect to the measured physical and material properties, suspension produced similar bone responses in male and female mice. The effects of suspension are manifested largely through geometric rather than through material changes.

Animals↗

Effect of oral calcium and calcium + fluoride treatments on mouse bone properties during suspension.

The bone effects of oral dosages of calcium chloride with or without supplementary sodium fluoride were assessed in antiorthostatically suspended mice. Two calcium dosages were used to replace half (3.1 mM) or all(6.3 mM) of the dietary calcium lost due to reduced food intake by the suspended mice. Two groups of 6.3 mM CaCl2-treated mice were additionally treated with 0.25 or 2.5 mM NaF. The results indicate that supplementation of the mouse drinking water with calcium salts prevents bone changes induced by short-term suspension, while calcium salts in combination with fluoride are less effective as fluoride dosage increases. However, the calcium supplements change the relationship between the femur mechanical properties and the mineral composition of the bone. Because of this, it appears that oral calcium supplements are effective through a mechanism other than simple dietary supplementation and may indicate a dependence of bone consistency on systemic and local fluid conditions.

Animals↗

Determining the efficacy of edge detection algorithms.

Edge detection is an important process in the interpretation of image data. Four types of edge detection algorithms (the Local Variance, Correlation, Laplacian and Frequency Peak algorithms) are compared for their ability to discriminate the edges present in an image with precisely defined edges. The variety of techniques are discussed in terms of their sensitivity to the presence of edges and their sensitivity to the applied noise. Both computational and empirical analyses are presented, and the relative merits of each discussed in terms of signal-to-noise ratio, sensitivity and computational difficulty. It is shown that local variance edge detection is an acceptable method for edge detection which simplifies the computation needed for image convolution. The means through which to devise more sophisticated edge detection algorithms is outlined, and the use of difference images to discriminate edges in an image is discussed. The results are also discussed in terms of the implementation of edge detection algorithms as part of a computer visual system which has an architecture modeled after the mammalian visual system.

Algorithms↗

Effect of localized pulsed electromagnetic fields on tail-suspension osteopenia in growing mice.

Pulsed magnetic fields (PEMFs) have been used effectively to treat bone fractures and sciatic-nerve-section-induced osteopenias. Properly applied PEMFs are presumed to stimulate osteogenesis. Mouse-tail suspension has been implemented as a means of inducing an osteopenic response in the long bones of the hind limbs. To evaluate localized PEMF effects, the mouse-suspension model was modified to accommodate the use of miniature wire coils affixed directly to the rear legs. Laterally and axially orientated PEMF effects were compared. Three test groups of mice included (C) control mice, (S) tail-suspended mice with treatment apparatus attached, and (SF) tail-suspended mice with apparatus attached and PEMFs delivered. The SF group was divided into mice receiving axial or lateral PEMFs. Significant bone changes occurred in suspended as compared with control mice after a 2-week test period. The PEMF mice showed significantly fewer osteopenic effects than did untreated, suspended mice. These findings are based on biomechanical measures of stiffness, strength, ductility, and energy as well as whole-bone mass and porosity. The effects of PEMFs on these properties differ for axial and lateral exposures. The results are discussed in terms of mechanisms underlying PEMF effects.

Animals↗