Reference equations for ultrasound bone densitometry of the radius in Central European children and adolescents.

UNLABELLED: Bone density measurements are important for evaluation and follow-up of children with alterations in their mineral status (increased risk for fractures and osteoporosis subsequently). Interpretation of these measurements relies on the availability of appropriate reference equations. We developed gender-specific, age-dependent reference values of bone density for Central European children. INTRODUCTION: In recent years, there has been an increasing demand for the measurement of bone density in children exposed to an increased risk of early alterations in their bone status. These values must be compared to an adequate reference population. The aim of the present study was to create reference equations of radial speed of sound (SOS) for Central European children and adolescents. METHODS: In this cross-sectional study, SOS values were measured at the distal third of the radius in 581 Swiss children and adolescents (321 girls and 260 boys) aged 6 to 16 years using the Sunlight Omnisense® 7000P quantitative ultrasound system. RESULTS: Gender-specific reference equations for SOS values were derived by polynomial regression and combined a cubic dependence of age and a linear dependence of height. The fitted SOS curves in our study population show a plateau period in both genders for younger ages followed by an increase phase beginning at the age of 12 in girls and 14 in boys. Neither the reported level of physical activity nor additional sport nor self-reported calcium intake influenced the reference equations. CONCLUSIONS: Our results show a good agreement with similar studies using the same measurement technique on other body parts, suggesting a wide applicability of the obtained reference curves over different European populations.

Maternal vitamin D intake during pregnancy increases gene expression of ILT3 and ILT4 in cord blood.

BACKGROUND: Recent studies indicate that prenatal vitamin D intake may protect against the development of atopic diseases in young children. Vitamin D has been shown to induce tolerogenic antigen-presenting cells such as dendritic cells. Whether the allergy-protective potential of prenatal vitamin D is mediated through such mechanisms is, however, unknown. OBJECTIVE: To evaluate the association between prenatal vitamin D supplementation and tolerogenic antigen-presenting cells in cord blood (CB) as determined by mRNA measurement of immunoglobulin-like transcripts (ILT)3 and ILT4. METHODS: A prospective multi-centre birth cohort was established in rural areas of five European countries. Information on maternal exposures including vitamin D intake was collected by questionnaires during pregnancy. The gene expression of ILT3 and ILT4 was analysed by real-time PCR in the CB of 927 children. Maternal vitamin D supplementation was assessed in Finland and France (n=349). RESULTS: Maternal vitamin D supplementation during pregnancy was associated with an increase in the gene expression of ILT3 (P=0.012) and ILT4 (P<0.001). This association remained significant for ILT4 (P=0.020) and showed a positive trend for the gene expression of ILT3 (P=0.059) after multivariate analysis controlling for various confounders. CONCLUSIONS: Vitamin D supplementation during pregnancy may increase the mRNA levels of ILT3 and ILT4 in CB. This finding may point towards an early induction of tolerogenic immune responses by maternal vitamin D intake.

Reference equations for lung function screening of healthy never-smoking adults aged 18-80 years.

The need for updated spirometric reference values to be used on European populations is widely acknowledged, especially for subjects aged >70 yrs. Their reference values are generally based on extrapolations. The aim of the present study was to calculate reference values for lung function screening of healthy, never-smoking adults aged 18-80 yrs and to compare them with the most widely used reference equations. Results of screening spirometry of 8,684 healthy, never-smoking adults were used to calculate mean values and fifth percentiles of lung function variables. The European Community of Coal and Steel (ECCS) reference equations underestimate forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). For example, in 50-yr-old males (height 175 cm), lower limits of normal for FEV(1) are underestimated by 198 mL, and for FVC by 210 mL. In 50-yr-old females (height 165 cm), lower limits of normal for FEV(1) are underestimated by 191 mL, and for FVC by 270 mL. The decline of FVC in elderly subjects is steeper than predicted by the ECCS. Reference equations derived from spirometry data locally collected in a practical setting by well-trained personnel might be more appropriate for everyday use than generally used equations based on data from scientific studies in the distant past.

TNF-alpha enhances intracellular glucocorticoid availability.

For understanding the mechanism(s) relating inflammation to corticosteroid action, the effect of tumour necrosis factor-alpha (TNF-alpha) on 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the enzyme regulating access of 11beta-hydroxycorticosteroids to receptors, was studied in LLC-PK(1) cells. We observed (i) NAD-dependent enzyme activity and mRNA for 11beta-HSD2, but not 11beta-HSD1, (ii) increasing 11beta-HSD2 activity with increasing degree of differentiation and (iii) a concentration-dependent down-regulation by TNF-alpha, phorbol myristate acetate (PMA) or glucose of activity and mRNA of 11beta-HSD2. The decrease of activity and mRNA by glucose and PMA, but not that by TNF-alpha, was abrogated by the protein kinase C inhibitor GF-109203X. The effect of TNF-alpha on 11beta-HSD2 was reversed by inhibiting the mitogen-activated protein kinases ERK with PD-098050 and p38 by SB-202190, or by activating protein kinase A with forskolin. Overexpression of MEK1, an ERK activator, down-regulated the 11beta-HSD2 activity. In conclusion, TNF-alpha decreases 11beta-HSD2 activity and thereby enhances glucocorticoid access to glucocorticoid receptors to modulate the inflammatory response.