Keisuke Sasagawa

Prediction of risk of fracture in the tibia due to altered bone mineral density distribution resulting from disuse: A finite element study

The disuse-related bone loss that results from immobilisation following injury shares characteristics with osteoporosis in post-menopausal women and the aged, with decreases in bone mineral density leading to weakening of the bone and increased risk of fracture. The aim of this study was to use the finite element method to: (i) calculate the mechanical response of the tibia under mechanical load and (ii) estimate of the risk of fracture; comparing between two groups, an able-bodied group and spinal cord injury patients group suffering from varying degrees of bone loss. The tibiae of eight male subjects with chronic spinal cord injury and those of four able-bodied age-matched controls were scanned using multi-slice peripheral quantitative computed tomography. Images were used to develop full three-dimensional models of the tibiae in Mimics (Materialise) and exported into Abaqus (Simulia) for calculation of stress distribution and fracture risk in response to specified loading conditions – compression, bending and torsion. The percentage of elements that exceeded a calculated value of the ultimate stress provided an estimate of the risk of fracture for each subject, which differed between spinal cord injury subjects and their controls. The differences in bone mineral density distribution along the tibia in different subjects resulted in different regions of the bone being at high risk of fracture under set loading conditions, illustrating the benefit of creating individual material distribution models. A predictive tool can be developed based on these models, to enable clinicians to estimate the amount of loading that can be safely allowed onto the skeletal frame of individual patients who suffer from extensive musculoskeletal degeneration (including spinal cord injury, multiple sclerosis and the ageing population). The ultimate aim is to reduce fracture occurrence in these vulnerable groups.

The Cooperativity of Human Fetal and Adult Hemoglobins is Optimized: A Consideration Based on the Effectiveness of the Bohr Shift

Abstract The physiological significance of the cooperativity of human hemoglobin (Hb) is considered from the viewpoint of the effectiveness of the Bohr shift at the sites of O2 release and uptake across the placental membrane. The effects of the Bohr shift was examined by changing the O2 saturation of Hb (S(pO2)) per unit change in P50, -dS(PO2)/dP50, where P50 is partial pressure of O2 at half saturation. The Bohr shift at the sites of O2 uptake and release was found to be highly effective in both fetal and maternal bloods at physiological degree of cooperativity (Hills coefficient, n=2.65). From the results obtained in this paper, it is concluded that the positions of OECs of fetal and maternal Hbs are regulated to receive a maximal benefit from the Bohr shift, and that a relatively low n value of human tetrameric Hb is adequate for the O2 and CO2 exchange across the placental membrane.

Influence of Allosteric Effectors and Temperature on Oxygen Binding Properties and the Bohr Effect of Bovine Hemoglobin

Abstract The O2 binding properties of bovine Hb were examined. The increase in Cl− and DPG concentration enhanced P50. A reduction in nmax was observed at high Cl− concentration, while DPG had little effect on nmax. An increase in Cl− concentration enhanced the Bohr effect, the magnitude of which reached a maximum at 0.1 M Cl− and 20°C. This concentration is nearly equal to that at the highest slope of the log P50 vs. log [Cl−] plot, and also equal to the physiological Cl− concentration (0.1 M) of bovine blood. Furthermore, the influence of Cl− concentration on the Bohr effect is independent of temperature. On the other hand, in the absence of Cl−, bovine Hb is sensitive to DPG; an increase in DPG concentration enhanced the Bohr effect, which reached a maximum at 3 mM DPG and 20°C. This concentration is nearly equal to that at the highest slope of the log P50 vs. log [DPG] plot. At low DPG concentrations, the DPG effect on the Bohr effect became small with increasing temperature, whereas at high DPG concentrations, the DPG effect was insensitive to temperature changes. At the physiological concentration of DPG (0.5 mM), increases in both Cl− concentration and temperature diminished the DPG effect. At the physiological concentrations of Cl− and DPG, the Bohr effect was −0.36 at 37°C. The ΔH value at the physiological concentrations of Cl− and DPG was approximately −5.8 kcal/mol at pH 7.4. These results indicate that Cl− and temperature are important determinants of the O2 binding properties of bovine Hb.

Significance of affinity and cooperativity in oxygen binding to hemoglobin of horse fetal and maternal blood

Abstract The physiological significance of the position and shape of the oxygen equilibrium curve (OEC) of horse hemoglobin (Hb) is considered from the viewpoint of oxygen (O2) transport efficiency and the effectiveness of the Bohr effect. In horse fetal and maternal bloods, their physiological O2 affinities are nearly optimized with respect to the effectiveness of the Bohr shift occurring at the O2 release site, when it is measured by the change in O2 saturation per unit change in P50. With relatively low cooperativity (n=2.69) of horse Hb under physiological conditions, the effectiveness of the Bohr shift for fetal blood at O2 uptake site and maternal blood at O2 release site is high. These facts imply that the position and the cooperativity of horse Hb OEC are optimized to receive maximal benefit from the double Bohr shift. Before exercise, the position of the OEC for adult mares is nearly optimized for the effectiveness of the Bohr shift occurring at the O2 release site, whereas, at maximal exercise, the position of the OEC tends to become advantageous for O2 transport efficiency.

A New Look on the Position of the Oxygen Equilibrium Curve of Human Adult Hemoglobin at Rest and during Exercise with Special Reference to the Effectiveness of the Bohr Shift

Abstract The position of oxygen equilibrium curve (OEC) for human adult Hb at rest is optimized with respect to the effectiveness of the Bohr shift which is measured by the change in O2 saturation at a venous O2 pressure of 40 torr per unit change in partial pressure of O2 at half saturation (dS(40)/dP50). The effectiveness of the Bohr shift at the physiological P50 of 27 torr depends on the cooperativity of O2 binding calculated by the Hill coefficient n, being maximized at n = 4. The effectiveness of the Bohr shift during exercise, which was expressed as dS(PvO2)/dP50, was the highest at the PvO2 (venous O2 pressure) of 28 torr. The effectiveness of the Bohr shift at PvO2 of 28 torr increased with increases n value (n value ranged from 2.65 to 3.27), while below PvO2 of 15 torr the opposite was true. As a whole, the position of the OEC of human adult Hb at rest is optimized with respect to the effectiveness of the Bohr shift while the efficiency of O2 delivery is moderately maintained. On the other hand, during exercise the position of the OEC is adjusted to make the efficiency of O2 delivery at high levels while the effectiveness of the Bohr shift is maintained at the same level as that at rest.

A finite element modelling for the tibia of a spinal cord injured patient

In paraplegia of Spinal Cord Injury (SCI), bone loss can occur rapidly and extensively in the paralysed lower limbs. It was reported that some patients develop osteoporosis in the tibia and femur even within the first year of injury [Coupaud et al, 2011]. Weakening of the bones after SCI is accompanied by a substantially increased risk of fracture. It is important to predict the most likely locations of fracture at regions of weakness along the bone in SCI. There is a clinical need to understand the macro-structural behaviour of the long bones in the body in order to develop potential physical treatments to tackle this musculoskeletal disorder in SCI patients. The aim of this ongoing study is to develop a modelling tool to help clinicians to quantify changes in bone structure and fracture susceptibility resulting from bone loss in the paralysed limbs after SCI.