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Biomedical subjects

C H Turner

Publications and source records attributed to C H Turner.

At least 19 recordsLinked to original sources
PubMed1992

The effects of fluoridated water on bone strength.

Fluoride from fluoridated water accumulates not only in the enamel of teeth but also in the skeleton. The effects of fluoridated water on the skeleton are not well understood, yet there is some evidence that fluoridated water consumption increases the incidence of fractures. In the present study, femoral bending strength was measured in rats on fluoride intakes that ranged from low levels to levels well above natural high fluoride drinking water. Bone strength followed a biphasic relationship with bone fluoride content. Fluoride had a positive effect on bone strength for lower fluoride intakes and a negative influence on bone strength for higher fluoride intakes. The vertebral fluoride content at which femoral strength was maximum was between 1,100 and 1,500 ppm. The increase in femoral strength at this fluoride level was not accompanied by an increase in femoral bone density. The optimal fluoride content is within the range of bone fluoride contents found in persons living in regions with fluoridated water (1 ppm) for greater than 10 years.

Animals↗
PubMed1992

Characterization of in vivo strain in the rat tibia during external application of a four-point bending load.

This paper describes a technique for characterizing strains and stresses induced in vivo in the rat tibia during application of an external four-point bending load. An external load was applied through the muscle and soft tissue with a four-point bending device, to induce strain in a 11 mm section of the right tibiae of ten adult female Sprague-Dawley rats. Induced strains were measured in vivo on the lateral surface of the tibia. Inter-rat difference, leg positioning and strain gage placement were evaluated as sources of variability of applied strains. Beam bending theory was used to predict externally induced in vivo strains. Finite element analysis was used to quantify the magnitude of shear stresses induced by this type of loading. There was a linear relationship between applied load and induced in vivo strains. In vivo strains induced by external loading were linearly correlated (R2 = 0.87) with the strains calculated using beam bending theory. The finite element analysis predicted shear stresses at less than 10% of the longitudinal stresses resulting from four-point bending. Strains predicted along the tibia by finite element analysis and beam bending theory were well-correlated. Inter-rat variability due to tibia size and shape difference was the most important source of variation in induced strain (CV = 21.6%). Leg positioning was less important (CV = 9.5%).

Animals↗
PubMed1992

On Wolff's law of trabecular architecture.

Several studies suggest that the yield strain in cancellous bone may be uniformly distributed and isotropic. Yield strain was reported to be independent of textural anisotropy in bovine cancellous bone [Turner, J. biomech. Engng 111, 1-5 (1989)] and it is plausible that yield strain is isotropic in human cancellous bone as well. In this paper, it is hypothesized that uniform, isotropic strain represents a goal of cancellous bone adaptation, i.e. cancellous bone alters its structure to maintain uniform, isotropic peak strains. Therefore, textural anisotropy must exactly cancel the anisotropy of the peak principal stresses imposed upon cancellous bone. When evaluating the relationships between mechanical properties of cancellous bone and trabecular architecture, it was found that over 90% of the variance of yield strength can be explained by one term--rho 2H3 (where rho is apparent density and H is the normalized anisotropy (fabric) constant). Furthermore, this single term explains 70-78% of the variance in Young's modulus of cancellous bone. Based upon these findings, it was postulated that fabric adaptation goes as Hi/Hj = [ sigma i/sigma j[, where Hi and Hj are fabric eigenvalues in the i- and the j-direction and sigma i and sigma j are peak principal stresses.

Adaptation, Physiological↗
PubMed1992

Functional determinants of bone structure: beyond Wolff's law of bone transformation.

Frost has suggested that functional loading controls bone mass and form as a thermostat controls temperature--by homeostatic regulation (i.e., by negative feedback). Yet, the literature contains many results that appear incompatible with the "mechanostat" hypothesis. We propose that a different type of regulation--epigenetic--is important in many aspects of bone adaptation. Epigenetic regulation, as we describe it, involves positive feedback loops and promotes differentiation as it forces elements of a system to choose between two extreme levels called attractors. Our review of bone adaptation data suggests that lamellar bone formation is regulated homeostatically, whereas the formation of woven-fibered bone or fracture callus is regulated epigenetically, that is, woven bone formation is brought about by a positive feedback loop that stimulates osteoblasts to a state of greater individual activity. This positive feedback loop may involve transforming growth factor beta (TGF beta), for which autocrine induction has been demonstrated in vivo, as well as other factors, including insulin-like growth factor (IGF) and prostaglandin E2 (PGE2). The importance of this model is that it provides a mechanism for many unexplained nonlinear events that have been observed in bone adaptation experiments. Furthermore, it provides insights into the genesis of woven bone, which is a critical step in the process of bone healing and regeneration.

Animals↗
PubMed1992

Structural changes in rat bone subjected to long-term, in vivo mechanical loading.

Woven bone formation is commonly observed when grossly altered loading conditions are imposed upon living bone tissue. The fate of this woven bone with time has not been fully characterized. In this study, rats underwent daily bending of the right tibia for a period of 3 to 14 weeks. New bone was formed in the region of maximum bending stresses on the right tibiae of all rats that underwent daily loading. The new bone was at first poorly mineralized with disorganized collagen structure. With time, the new bone consolidated into a well mineralized primary bone structure similar in appearance to pre-existing nonlamellar bone within the tibial cortex. Using the data from this study and previous studies, we were able to outline the sequence of events that occur during bone adaptation in the rat tibia loading model. Explosive new woven bone formation began to occur five days after the initial four-point bending session, and the amount of woven bone reached a peak after about 15 days. After the third week the new bone began to consolidate. Rapid mineralization occurred during the third and fourth weeks, with less rapid mineralization occurring for several weeks thereafter. After the 14 weeks, the new bone was fully mineralized, and new bone formation had stopped.

Animals↗
PubMed1991

Toward a cure for osteoporosis: reversal of excessive bone fragility.

While estrogen replacement therapy and calcium supplementation appear to be effective at preventing postmenopausal osteoporosis, therapy for established osteoporosis is far less effective. The reduction of bone fragility should be a goal of a treatment for established osteoporosis. To this end, increases in cortical bone mass by subperiosteal new bone formation may produce the greatest mechanical advantage. Anti-resorptive drugs, such as etidronate, have shown potential for reducing the incidence of osteoporotic fracture in the short term, but their ability to produce a long-term benefit may be limited. An alternative approach might be to develop drug therapies that substantially increase cortical bone strength, namely by stimulating periosteal bone formation. Although sodium fluoride has proved to be problematic, there are several other potential osteoporosis therapies. They include treatment with anabolic hormones (e.g. growth hormone and anabolic steroids) and targeted delivery of growth factors. Also, anti-resorptive and formation-stimulating drugs might be combined in a new form of ADFR (coherence) therapy where the new acronym means: Activate-Depress-Formation stimulation-Repeat.

Bone Remodeling↗
PubMed1991

Ultrasonic velocity as a predictor of strength in bovine cancellous bone.

Ultrasonic methods measure properties intrinsic to bone's structure that are not necessarily dependent on bone mass. Therefore, ultrasound may prove to be a useful tool for diagnosing bone fragility and osteoporosis. The goal of this study was to determine the relationship between apparent velocity of ultrasound (AVU) measured using the OsteoTechnology prototype I machine and cancellous bone yield strength (sigma y). AVU correlated well with sigma y (r = 0.753). Consistent with theory, the best predictor of cancellous bone strength was the combination of apparent density (rho a) and AVU, rho a (AVU)2, which had an r2 of 77.4%.

Animals↗
PubMed1991

A noninvasive, in vivo model for studying strain adaptive bone modeling.

We present a noninvasive, in vivo model for strain application in the tibiae of rats. The hind limb of each animal was placed into a device that applied four point bending to the tibia. Bending was applied in the medial-lateral direction causing compression on the lateral surface of the tibia and tension on the anteromedial surface. The peak strain magnitudes were estimated to be between 1600 and 3500 mu strain. In this pilot work, data were collected from 12 rats. The rats received either one cycle per day, four cycles per day, 12 cycles per day, 36 cycles per day, or 108 cycles per day of bending. The experimental (right) tibiae from all of the rats showed new bone formation after 12 days. The control (left) tibiae showed no new bone formation over this period. A better organized, dense bony reaction occurred in regions of lesser strains than in regions of higher strains, where there was a large accumulation of bone easily identified as woven. The organization and density of the newly formed bone appeared to be inversely related to the peak strains in the region. After 40 days of daily loading, the new bone area appeared to be more compact and better mineralized. However, bone formation was still occurring after 40 days. The results of this study suggest that woven bone formation occurred due to the bending stimulus and not due to pathology.

Adaptation, Physiological↗
PubMed1991

Homeostatic control of bone structure: an application of feedback theory.

The regulation of bone mass and structure in the weight-bearing skeleton is governed to a great extent by the mechanical demands placed upon the bone tissue. The apparent biological goal is the maintenance of a minimum adequate structure, in which the margin of safety between normal mechanical demands and fracture is balanced by the cost of excessive bone mass on mobility. Frost has developed two powerful postulates concerning bone adaptation: (a) there exist threshold levels of mechanical strain, above or below which bone adaptation is turned on, and (b) the set point for normal bone structure can be modulated by hormones. A model was developed, using Frost's postulates and simple feedback theory, that describes the interaction between biochemical influences and mechanical influences on bone structure. The model predicts that biochemical agents that influence bone structure independently of the mechanical feedback system (e.g., calcitonin) are capable of only limited anabolic effects on bone mass because their influences conflict with mechanical influences. However, biochemical agents that influence bone structure by changing the set point of the mechanical feedback system (e.g., estrogen) will provide lasting changes in bone structure. Age-related changes occur within the effector and transduction components of the mechanical feedback system that tend to make it sluggish. These changes may lead to increased bone fragility because the system is no longer capable of maintaining adequate bone structure.

Adaptation, Physiological↗
PubMed1990

1H-n.m.r. studies of the isolated activation segment from pig procarboxypeptidase A.

The isolated activation segment (asA) from pig pancreatic procarboxypeptidase A was studied by 1H-n.m.r. spectroscopy over a wide range of solution conditions. Isolated asA shows many characteristics of compactly folded globular proteins, such as the observation of perturbed positions for resonances from methyl groups, alpha-carbon atoms, histidine residues and the tyrosine residue. The single tyrosine residue (Tyr-70) exhibits a very high pKa, and both histidine and tyrosine residues show slow chemical modification (deuteration and iodination). In contrast, asA shows rapid NH exchange. Analysis of the spectra by pH titration and nuclear Overhauser effects revealed several residue interactions. Quantitative analysis of deuterium and tritium exchange allowed the assignment of the histidine C-2-H resonances to their respective residues in the sequence. His-66, the closest to the sites of proteolytic attack in the proenzyme, is shown to be the most accessible to solvent in procarboxypeptidase A. It was also shown that asA is thermally very stable ['melting' temperature (Tm) 88 degrees C] and requires a high urea concentration for denaturation (6.25 M, at pH 7.5). Evidence is presented for some degree of conformational flexibility in the premelting range, a feature that could be ascribed to the preponderance of helical secondary structure and to the lack of disulphide bridges. The free solution structure of asA is probably unchanged when it binds to carboxypeptidase A.

Animals↗
PubMed1990

Potential of a soluble tetrazolium/formazan assay for the evaluation of filarial viability.

Using female Acanthocheilonema viteae we have investigated the bioreduction of the tetrazolium reagent XTT (2,3-bis(2-methoxy-4-nitro-sulphonyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide). Unlike the formazan formed by other tetrazolium salts, that derived from XTT readily diffuses out of A. viteae in vitro. Formazan formation can therefore be quantified by direct absorbance reading of the incubation medium, eliminating the need for a DMSO solubilization step. Optimum assay conditions involved a 4 h incubation, in the presence of the electron coupling agent phenazine methosulphate (PMS). Repeat 4 h incubations with XTT-PMS were well tolerated by worms for 5 consecutive days. This confirmed the low toxicity of XTT formazan and its usefulness in the semi-continuous assessment of filarial viability. In comparison to our previously reported MTT (3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide)-reduction assay XTT-PMS reduction showed comparable drug sensitivity and accuracy, however XTT-PMS appears to be at least 10-15 times less efficiently reduced by A. viteae females. A possible application of the XTT assay using female Onchocerca volvulus is discussed.

Animals↗
PubMed1990

The fabric dependence of the orthotropic elastic constants of cancellous bone.

It has been proposed that the orthotropic elastic constants of cancellous bone depend upon a tensorial measure of anisotropy called fabric as well as the tissue's structural density. Cowin (1985, Mechanics Mater, 4, 137-147; 1986, J. biomech. Engng 108, 83-88) developed explicit relationships for the elastic constant, structural density and fabric relationship. In this study the orthotropic elastic moduli, structural density, and fabric components were measured for 11 cancellous bone specimens from five bovine femora and for 75 specimens from three human proximal tibiae and fitted to these relationships using a least squares analysis. The relationships explained between 72 and 94% of the variance in the elastic constants. The relationships between the elastic constants and squared or cubed power functions of structural density had better predictive value over the entire distribution of the data than did expressions with linear functions of structural density.

Aged↗
PubMed1989

Colorimetric quantitation of filarial viability.

A simple three-step colorimetric assay based on the tetrazolium salt MTT (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) has been developed for quantifying filarial viability. Living (but not dead) filariae take up MTT and rapidly reduce it to formazan, so staining themselves dark blue. This colour change which is easily seen provides a rapid qualitative test for filarial viability. Quantitative data can be obtained by solubilizing formazan out of the worm with DMSO and measuring the absorbance of the resulting solution at 510 nm. To date the technique has been demonstrated in several species of filariae including Onchocerca volvulus. MTT reduction is thought to be selective for NADH-dependent dehydrogenase activity in viable worms. The reaction occurs readily in all developmental stages of Dipetalonema viteae including fragments of filarial tissue. Enzyme activity in viable intact D. viteae appears to be primarily associated with the hypodermis/muscle cells, with minimal formazan formation in the gut and reproductive tracts. The application of this MTT assay as a parameter for quantifying in vitro drugs effects is described. Assay procedures have been developed and optimized with D. viteae and Brugia pahangi for the assessment of effects of macrofilariae and microfilarial release, and the activity of a range of antifilarial standards reported. Several potential applications of the technique to studies on filarial biology are discussed.

Animals↗
PubMed1989

Anatomical variation of orthotropic elastic moduli of the proximal human tibia.

The anatomical variation of orthotropic elastic moduli of the cancellous bone from three human proximal tibiae was investigated using an ultrasonic technique. With this technique, it was possible to measure three orthogonal elastic moduli and three shear moduli from cubic specimens of cancellous bone as small as 8 mm per side. Correlation with mechanical tensile testing has shown this technique to offer a precise measure of cancellous modulus (Eten = 0.94Eult + 144.6 MPa, r2 = 0.96, n = 34). The cancellous bone of the proximal tibia was found to be very inhomogeneous, with the axial modulus ranging between 340 and 3350 MPa. A course map is presented, showing measured Young's moduli as a function of anatomical position. The anisotropy of the cancellous bone, determined by the relative differences between the three orthogonal moduli, was shown to be relatively constant over the entire range of cancellous densities tested. The relationship between the axial elastic modulus and the apparent density was found to be approximately linear, as reported by others for proximal tibial cancellous bone.

Aged↗
PubMed1989

A "minimal epitope" anti-protein antibody that recognises a single modified amino acid.

Antibodies that recognise proteins bind to epitopes of varying size, but a grouping of the order of six amino acids, contiguous or not, is regarded as a typical number. By using as immunogen a highly abundant and universal eukaryotic nuclear protein (histone H4) modified in a manner not typical of secreted proteins (acetylation of lysine side chains), antiserum has been raised in rabbits having the single amino acid epsilon-N-acetyl lysine as the recognition epitope. The affinity-purified antibody should be useful for studying the functional role of this modification. The methodology has potential for raising antibodies to other types of post-translationally modified proteins.

Animals↗
PubMed1989

Yield behavior of bovine cancellous bone.

The compressive yield strain was measured for 61 specimens of bovine cancellous bone from three distal femora. There was no significant relationship (p = 0.08, R2 = 0.051) between yield strain and the degree of trabecular orientation. There was a significant positive correlation (p less than 0.00001, R2 = 0.319) between yield strain and structural (apparent) density and significant negative correlation (p less than 0.0025, R2 = 0.145) between yield strain and bone density. Yield strain correlated best with bone solid volume fraction Vv (epsilon y = 0.592 +2- 1.446vv, R2 = 0.337). The quantity, yield strain, is highly dependent on specific definitions of the yield point and the point of zero strain. For this study the yield point was defined by a 0.0003 offset criterion, and the point of zero strain was defined as the point where the tangent at 15 percent of yield crosses zero. The results using these definitions were compared with results using yield strain values determined by other definitions of the yield point and zero strain. The correlations between yield strain and trabecular orientation, structural density and bone density changed very little for differing definitions of yield. The results suggest that yield strain in cancellous bone is isotropic or independent of textural anisotropy, so the yield behaviour may be characterized by a maximum strain yield criterion. The results also suggest that the primary mode of yield in cancellous bone is buckling of the trabeculae.

Animals↗