Structural parameters of normal and osteoporotic human trabecular bone are affected differently by microCT image resolution.

UNLABELLED: This study employed microCT to investigate whether image resolution affects bone structural parameters differently in healthy normal and osteoporotic trabecular bone. With increasing image voxel size, the originally detected differences between sample groups diminished. The results suggest that structural differences may not be reliably detected with clinical scanners. INTRODUCTION: Structural parameters of bone reflect its health status, but are highly dependent on the image resolution. We hypothesized that image resolution affects bone structural parameters differently in normal and osteoporotic trabecular bone. METHODS: Human trabecular bone samples from the iliac crest and the knee were analyzed (normal n = 11, osteoporotic n = 15) using a high-resolution microCT (14 or 18 µm voxel sizes). Images were re-sampled to voxel sizes 1-16 times larger than the original image and thresholded with global or local adaptive algorithms. Absolute and normalized values of each structural parameter were calculated, and the effect of decreasing image resolution was compared between the normal and osteoporotic samples. RESULTS: Normal and osteoporotic samples had different (p < 0.05) absolute bone volume fractions. However, the normalized values showed that the osteoporotic samples were more prone to errors (p < 0.05) with increased voxel size. The absolute values of trabecular number, trabecular separation, degree of anisotropy, and structure model index were different between the groups at the original voxel size (p < 0.05), but at voxel sizes between 60 and 110 µm, those differences were no longer significant. CONCLUSIONS: The results suggest that structural differences between osteoporotic and normal trabecular bone may not be reliably detected with clinical CT scanners providing image voxel sizes above 100 µm.

Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study.

AIM: To evaluate the efficacy and safety of the potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin administered as add-on therapy to metformin in patients with type 2 diabetes with inadequate glycaemic control. METHODS: This 24-week, randomized, placebo-controlled, double-blind, parallel-group study was carried out in 82 centres in 10 countries. Patients with HbA1c levels of 7.0-10.0% on metformin and a maximum of one additional antidiabetes medication, which was discontinued at screening, continued on metformin ≥1500 mg/day for 6 weeks, including a placebo run-in period of 2 weeks, before being randomized to linagliptin 5 mg once daily (n = 524) or placebo (n = 177) add-on. The primary outcome was the change from baseline in HbA1c after 24 weeks of treatment, evaluated with an analysis of covariance (ANCOVA). RESULTS: Mean baseline HbA1c and fasting plasma glucose (FPG) were 8.1% and 9.4 mmol/l, respectively. Linagliptin showed significant reductions vs. placebo in adjusted mean changes from baseline of HbA1c (-0.49 vs. 0.15%), FPG (-0.59 vs. 0.58 mmol/l) and 2hPPG (-2.7 vs. 1.0 mmol/l); all p < 0.0001. Hypoglycaemia was rare, occurring in three patients (0.6%) treated with linagliptin and five patients (2.8%) in the placebo group. Body weight did not change significantly from baseline in both groups (-0.5 kg placebo, -0.4 kg linagliptin). CONCLUSIONS: The addition of linagliptin 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin resulted in a significant and clinically meaningful improvement in glycaemic control without weight gain or increased risk of hypoglycaemia.

Longitudinal elastic properties and porosity of cortical bone tissue vary with age in human proximal femur.

Tissue level structural and mechanical properties are important determinants of bone strength. As an individual ages, microstructural changes occur in bone, e.g., trabeculae and cortex become thinner and porosity increases. However, it is not known how the elastic properties of bone change during aging. Bone tissue may lose its elasticity and become more brittle and prone to fractures as it ages. In the present study the age-dependent variation in the spatial distributions of microstructural and microelastic properties of the human femoral neck and shaft were evaluated by using acoustic microscopy. Although these properties may not be directly measured in vivo, there is a major interest to investigate their relationships with the linear elastic measurements obtained by diagnostic ultrasound at the most severe fracture sites, e.g., the femoral neck. However, before the validity of novel in vivo techniques can be established, it is essential to understand the age-dependent variation in tissue elastic properties and porosity at different skeletal sites. A total of 42 transverse cross-sectional bone samples were obtained from the femoral neck (Fn) and proximal femoral shaft (Ps) of 21 men (mean±SD age 47.1±17.8, range 17-82years). Samples were quantitatively imaged using a scanning acoustic microscope (SAM) equipped with a 50MHz ultrasound transducer. Distributions of the elastic coefficient (c33) of cortical (Ct) and trabecular (Tr) tissues and microstructure of cortex (cortical thickness Ct.Th and porosity Ct.Po) were determined. Variations in c33 were observed with respect to tissue type (c33Trc33(Ct.Fn)=35.3GPa>c33(Tr.Ps)=33.8GPa>c33(Tr.Fn)=31.9GPa), and cadaver age (R(2)=0.28-0.46, p<0.05). Regional variations in porosity were found in the neck (superior 13.1%; inferior 6.1%; anterior 10.1%; posterior 8.6%) and in the shaft (medial 9.5%; lateral 7.7%; anterior 8.6%; posterior 12.0%). In conclusion, significant variations in elastic coefficients were detected between femoral neck and shaft as well as between the quadrants of the cross-sections of neck and shaft. Moreover, an age-related increase in cortical porosity and a stiffening of the bone tissue were observed. These findings may explain in part the increase in susceptibility to suffer low energy fractures during aging and highlight the potential of ultrasound in clinical osteoporosis diagnostics.

Microfiling and automatic filing of radiographs.

When advantage is taken of the newest qualities of microfilms and copy films and when using their special developers and developing machines, it seems today that the microfilming of radiographs on 35 mm film is successful. Equipment in the price range of 67 000 DM is available. It includes automated filming and developing, but slipping microfilms onto the punch card jackets is semi-automatic. The advantage of the equipment is its low price, its small size compared to the Delcomat system, and thus its smaller filing space need. Also, the automation of filing is possible with this system. The system seems to be quite suitable for at least creating and maintenance of teaching files.

Ectopic expression of ABI3 gene enhances freezing tolerance in response to abscisic acid and low temperature in Arabidopsis thaliana.

The plant hormone abscisic acid (ABA) regulates several physiological and developmental processes in plants, including stress adaptation and seed maturation. ABA-mediated processes appear to be central in plant cold acclimation and expression of cold acclimation-related genes. Ectopic expression of ABI3 encoding a seed-specific transcriptional activator confers on Arabidopsis vegetative tissues the ability to accumulate seed-specific transcripts in response to ABA, and also influences some ABA-mediated vegetative responses. In the present study we characterized the effect of ectopic expression of ABI3 on cold acclimation and development of freezing tolerance in Arabidopsis. We first determined the effect of ABI3 on ABA-induced expression of cold acclimation-related genes. Expression of ABI3 increased the ABA-induced accumulation of transcripts for several ABA/cold/drought-responsive genes such as RAB18 and LTI78. Enhanced expression of these genes was evident even after transient application of ABA, and the enhanced expression was correlated with increased freezing tolerance in ABI3 transgenic plants. Ectopic expression of ABI3 also appeared to modulate low temperature-induced freezing tolerance. The ABI3 transgenic plants acclimated faster than the wild-type plants, and the maximum tolerance obtained was significantly higher. These data showed that lower levels of ABA were needed to trigger the expression of the genes and to maintain the freezing-tolerant state in the ABI3 transgenic plants, and indicate that ectopic expression of ABI3 leads to enhanced responsiveness to ABA. The ectopic expression of ABI3 could provide a new strategy for engineering plant stress tolerance.