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Background: The high risk of fracture associated with chronic spinal cord injury (SCI) is attributed to extensive disuse-related bone loss in previously weight-bearing long bones. Changes in bone mineral density (BMD) after SCI have been documented extensively for the epiphyses of the tibia and femur, fracture-prone sites in this patient group. Less attention has been given to patterns of cortical bone loss in the diaphyses, but variability in BMD distributions throughout the long bones may contribute to some patients’ increased susceptibility to shaft fractures in chronic SCI. Aim: A cross-sectional study was carried out to determine whether BMD distributions along the tibia differ between individuals with chronic SCI and healthy able-bodied (AB) controls, in both the trabecular and cortical bone compartments. The effects of time post-injury and gender on BMD distribution were also explored. Methods: Individuals with chronic (≥ 6 months post-injury) motor-complete SCI were recruited from the Queen Elizabeth National Spinal Injuries Unit (Glasgow, UK). AB control subjects were recruited to achieve similar age and gender profiles for the SCI and control groups. Multi-slice pQCT (XCT3000, Stratec) was performed along the length of the tibia (2mm thickness, 0.5mm voxel size), at 1% intervals in the epiphyses and 5% intervals in the diaphysis (34 slices in total). These were used to reconstruct full 3-D subject-specific models (Mimics, Materialise) of BMD distribution, by interpolating between slices. Subjects with chronic SCI were subdivided into ‘early’ (

The O2 binding properties of bovine Hb were examined. The increase in Cl- and DPG concentration enhanced P50. A reduction in n(max) was observed at high Cl- concentration, while DPG had little effect on n(max). An increase in Cl- concentration enhanced the Bohr effect, the magnitude of which reached a maximum at 0.1 M Cl- and 20 degrees 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 degrees 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 degrees C. The deltaH 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.

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 O(2) release and uptake across the placental membrane. The effects of the Bohr shift was examined by changing the O(2) saturation of Hb (S(pO2)) per unit change in P(50), -dS(PO2)/d P(50), where P(50) is partial pressure of O(2) at half saturation. The Bohr shift at the sites of O(2) uptake and release was found to be highly effective in both fetal and maternal bloods at physiological degree of cooperativity (Hill's 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 O(2) and CO(2) exchange across the placental membrane.

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 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...

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.