Allopurinol and oxypurinol promote osteoblast differentiation and increase bone formation

AbstractAllopurinol and its active metabolite, oxypurinol are widely used in the treatment of gout and hyperuricemia. They inhibit xanthine oxidase (XO) an enzyme in the purine degradation pathway that converts xanthine to uric acid. This investigation examined the effect of allopurinol and oxypurinol on bone formation, cell number and viability, gene expression and enzyme activity in differentiating and mature, bone-forming osteoblasts. Although mRNA expression remained relatively constant, XO activity decreased over time with mature osteoblasts displaying reduced levels of uric acid (20% decrease). Treatment with allopurinol and oxypurinol (0.1–1µM) reduced XO activity by up to 30%. At these concentrations, allopurinol and oxypurinol increased bone formation by osteoblasts ~4-fold and ~3-fold, respectively. Cell number and viability were unaffected. Both drugs increased tissue non-specific alkaline phosphatase (TNAP) activity up to 65%. Osteocalcin and TNAP mRNA expression was increased, 5-fold and 2-fold, respectively. Expression of NPP1, the enzyme responsible for generating the mineralisation inhibitor, pyrophosphate, was decreased 5-fold. Col1α1 mRNA expression and soluble collagen levels were unchanged. Osteoclast formation and resorptive activity were not affected by treatment with allopurinol or oxypurinol. Our data suggest that inhibition of XO activity promotes osteoblast differentiation, leading to increased bone formation in vitro

Waist circumference and waist-to-height ratio of Hong Kong Chinese children

<p>Abstract</p> <p>Background</p> <p>Central body fat is a better predictor than overall body fat for cardiovascular (CV) risk factors in both adults and children. Waist circumference (WC) has been used as a proxy measure of central body fat. Children at high CV risk may be identified by WC measurements. Waist-to-height ratio (WHTR) has been proposed as an alternative, conveniently age-independent measure of CV risk although WHTR percentiles have not been reported. We aim to provide age- and sex-specific reference values for WC and WHTR in Hong Kong Chinese children.</p> <p>Methods</p> <p>Cross sectional study in a large representative sample of 14,842 children aged 6 to 18 years in 2005/6. Sex-specific descriptive statistics for whole-year age groups and smoothed percentile curves of WC and WHTR were derived and presented.</p> <p>Results</p> <p>WC increased with age, although less after age 14 years in girls. WHTR decreased with age (particularly up to age 14). WHTR correlated less closely than WC with BMI (r = 0.65, 0.59 cf. 0.93, 0.91, for boys and girls respectively).</p> <p>Conclusion</p> <p>Reference values and percentile curves for WC and WHRT of Chinese children and adolescents are provided. Both WC and WHTR are age dependent. Since the use of WHRT does not obviate the need for age-related reference standards, simple WC measurement is a more convenient method for central fat estimation than WHRT.</p

Racial differences in central adiposity in a longitudinal cohort of black and white adolescent females

<p>Abstract</p> <p>Background</p> <p>Central adiposity is related to chronic disease risk in adolescents. Racial differences in waist circumference have been identified using cross-sectional data from this age group. We tested for racial differences in age-related growth in waist circumference in a longitudinal cohort of black and white adolescent girls.</p> <p>Methods</p> <p>We analyzed 9 years of publicly available data from the National Heart, Lung, and Blood Institute Growth and Health Study, for 2379 girls (1213 black and 1166 white) enrolled at age 9-10 years in 1987-1988 and followed annually. Individual growth trajectories of waist circumference were constructed for girls with >3 annual measures. Mixed models were used to compare changes in waist circumference during adolescence between black and white females. BMI and age at menarche were included in the models.</p> <p>Results</p> <p>At each age, black females had significantly higher waist circumference. Mean annual increase in waist circumference was significantly higher for black females compared to white females (1.46 cm/yr vs. 1.36 cm/yr, respectively). After adjusting for BMI, the mean annual increase in waist circumference for white females was significantly higher than for black females (0.08 cm/yr vs. -0.07 cm/yr, respectively). These relationships remained significant after adjusting for age at menarche.</p> <p>Conclusions</p> <p>Black females had significantly steeper increases in waist circumference over adolescence than white females. After adjusting for BMI and age at menarche, however, the annual increase in waist circumference for black females was significantly shallower than for their white peers. These data suggest racial differences in the deposition of fat over the adolescent period.</p

Extended Interferon-Alpha Therapy Accelerates Telomere Length Loss in Human Peripheral Blood T Lymphocytes

BACKGROUND: Type I interferons have pleiotropic effects on host cells, including inhibiting telomerase in lymphocytes and antiviral activity. We tested the hypothesis that long-term interferon treatment would result in significant reduction in average telomere length in peripheral blood T lymphocytes. METHODS/PRINCIPAL FINDINGS: Using a flow cytometry-based telomere length assay on peripheral blood mononuclear cell samples from the Hepatitis-C Antiviral Long-term Treatment against Cirrhosis (HALT-C) study, we measured T cell telomere lengths at screening and at months 21 and 45 in 29 Hepatitis-C virus infected subjects. These subjects had failed to achieve a sustained virologic response following 24 weeks of pegylated-interferon-alpha plus ribavirin treatment and were subsequently randomized to either a no additional therapy group or a maintenance dose pegylated-IFNalpha group for an additional 3.5 years. Significant telomere loss in naive T cells occurred in the first 21 months in the interferon-alpha group. Telomere losses were similar in both groups during the final two years. Expansion of CD8(+)CD45RA(+)CD57(+) memory T cells and an inverse correlation of alanine aminotransferase levels with naive CD8(+) T cell telomere loss were observed in the control group but not in the interferon-alpha group. Telomere length at screening inversely correlated with Hepatitis-C viral load and body mass index. CONCLUSIONS/SIGNIFICANCE: Sustained interferon-alpha treatment increased telomere loss in naive T cells, and inhibited the accumulation of T cell memory expansions. The durability of this effect and consequences for immune senescence need to be defined

Telomere Length as a Biomarker for Adiposity Changes after a Multidisciplinary Intervention in Overweight/Obese Adolescents: The EVASYON Study

[Context] Telomeres are biomarkers of biological aging. Shorter telomeres have been associated with increased adiposity in adults. However, this relationship remains unclear in children and adolescents. [Objective] To evaluate the association between telomere length (TL) and adiposity markers in overweight/obese adolescents after an intensive program. We hypothesize that greater TL at baseline would predict a better response to a weight loss treatment. Design, Setting, Patients and Intervention The EVASYON is a multidisciplinary treatment program for adolescents with overweight and obesity that is aimed at applying the intervention to all possibly involved areas of the individual, such as dietary habits, physical activity and cognitive and psychological profiles. Seventy-four participants (36 males, 38 females, 12–16 yr) were enrolled in the intervention program: 2 months of an energy-restricted diet and a follow-up period (6 months). [Main Outcome] TL was measured by quantitative real-time polymerase chain reaction at baseline and after 2 months; meanwhile, anthropometric variables were also assessed after 6 months of follow-up. [Results] TL lengthened in participants during the intensive period (+1.9±1.0, p<0.001) being greater in overweight/obese adolescents with the shortest telomeres at baseline (r = −0.962, p<0.001). Multivariable linear regression analysis showed that higher baseline TL significantly predicted a higher decrease in body weight (B = −1.53, p = 0.005; B = −2.25, p = 0.047) and in standard deviation score for body mass index (BMI-SDS) (B = −0.22, p = 0.010; B = −0.47, p = 0.005) after the intensive and extensive period treatment respectively, in boys. [Conclusion] Our study shows that a weight loss intervention is accompanied by a significant increase in TL in overweight/obese adolescents. Moreover, we suggest that initial longer TL could be a potential predictor for a better weight loss response.Research relating to this work was funded by grants from the Health Research Fund from the Carlos III Health Institute from Ministry of Health and Consumption, Fondo de Investigación Sanitaria (FIS; PI051579, PI051080) for the EVASYON project; Línea Especial, Nutrición y Obesidad (University of Navarra); Spanish Ministry of Science and Innovation (MICINN) [SAF2010-20367]; Carlos III Health Institute [Centro de Investigación Biomédica en Red (CIBER) project, CB06/03/1017], and RETICS network. The scholarship to S. García-Calzón from the FPU ‘Formación de Profesorado Universitario’ from the Spanish Ministry is fully acknowledged

Atypical BECTS and homocystinuria

Abstract Reported is an association of atypical benign childhood epilepsy with centrotemporal spikes (BECTS) and homocystinuria in three apparently healthy children with borderline intelligence, two of whom had difficult-to-control seizures. In all three, EEG were suggestive of BECTS, although the clinical features were not. Homocystinuria could not be diagnosed for several years, pending metabolic evaluation. PMID:14581679[PubMed - indexed for MEDLINE