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Introduction: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed. Methods: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min. Plasma and dialysate concentrations of FGF23 sclerostin, osteoprotegerin, and osteocalcin were measured at 1, 2, 4, 6, and 8 h permitting the estimation of dialysis clearance. Results: Clearance of FGF23 was 7.7 mL/min, of sclerostin was 7.6 mL/min, of osteoprotegerin was 1.2 mL/min, and of osteocalcin was 19.7 mL/min. Clearance of FGF23 was correlated to sclerostin and osteoprotegerin clearance and also to the ultrafiltration rate. Although, osteocalcin blood concentrations decreased during dialysis, they rebounded within 6 h. Overall, no significant changes in blood concentrations of the measure mineral bone metabolism factors were observed. Conclusions: The intradialytic clearance of osteocalcin, FGF23, sclerostin, and osteoprotegerin occurs; however, only clearance of FGF23 is directly correlated with the ultrafiltration rate. The effects of dialytic clearance on mineral bone metabolism are, however, uncertain and intradialytic plasma concentrations of the studied substrates remained largely unchanged. [ABSTRACT FROM AUTHOR]

Fructose has recently been observed to affect brain metabolism and cognitive function in adults. Yet, possible late-onset effects by gestational fructose exposure have not been examined. We evaluated mitochondrial function in the brain of aging (15 months) male offspring of Fischer F344 rat dams fed a high-fructose diet (50% energy from fructose) during gestation and lactation. Maternal fructose exposure caused a significantly lower body weight of the offspring throughout life after weaning, while birth weight, litter size, and body fat percentage were unaffected. Isolated brain mitochondria displayed a significantly increased state 3 respiration of 8%, with the substrate combinations malate/pyruvate, malate/pyruvate/succinate, and malate/pyruvate/succinate/rotenone, as well as a significant decrease in the P/O2 ratio, compared with the control. Uncoupling protein 5 (UCP5) protein levels increased in the fructose group compared with the control (P=0.03) and both UCP5 mRNA and protein levels were inversely correlated with the P/O2 ratio (P=0.008 and 0.03, respectively), suggesting that UCP5 may have a role in the observed decreased phosphorylation efficiency. In conclusion, maternal high-fructose diet during gestation and lactation has long-term effects (fetal programming) on brain mitochondrial function in aging rats, which appears to be linked to an increase in UCP5 protein levels. [ABSTRACT FROM AUTHOR]

âExtreme diets consisting of either high fat (HF) or high sucrose (HS) may lead to insulin resistance in skeletal muscle, often associated with mitochondrial dysfunction. However, it is not known if these diets alter normal interactions of pyruvate and fatty acid oxidation at the level of the mitochondria. Here, we report that rat muscle mitochondria does show the normal Randletype fat-carbohydrate interaction seen in vivo. The mechanism behind this metabolic flexibility at the level of the isolated mitochondria is a regulation of the flux-ratio: pyruvate dehydrogenase (PDH)/β-oxidation to suit the actual substrate availability, with the PDH flux as the major point of regulation. We further report that this regulatory mechanism of carbohydrate-fat metabolic interaction surprisingly is lost in mitochondria obtained from animals exposed for 12 weeks to a HF- or a HS diet as compared to rats given a normal chow diet. The mechanism seems to be a loss of the PDH flux decrease seen in controls, when fatty acid is supplied as substrate in addition to pyruvate, and vice versa for the supply of pyruvate as substrate to mitochondria oxidizing fatty acid. Finally, we report that the calculated TCA flux in the isolated mitochondria under these circumstances shows a significant reduction (~50%) after the HF diet and an even larger reduction (~75%) after the HS diet, compared with the chow group. Thus, it appears that obesogenic diets as those applied here have major influence on key metabolic performance of skeletal muscle mitochondria. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Retinol-Binding Protein 4 and Insulin Resistance in Lean, Obese, and Diabetic Subjects," by T. E. Graham, Q. Yang, et al in the 2006 issue.

Calprotectin comprises more than 45% of the cytosolic content of neutrophil granulocytes. Because pathogenesis, disease activity and disease progression in COPD are believed to be partly dependent of neutrophil driven inflammation we decided to investigate whether plasma level of calprotectin (p-calprotectin) was associated with all-cause mortality in patients with COPD. We measured p-calprotectin in blood samples from 460 patients with moderate to very severe COPD in stable phase. Patients were stratified into three groups according to p-calprotectin level. Outcome measure was all-cause mortality. Analyses were adjusted for factors known to influence mortality using a Cox regression analysis. We found a time dependent correlation between p-calprotectin levels and mortality during the first 5 years of follow-up. Increasing levels of p-calprotectin were associated with concomitant increases in mortality from HR 1.56 (CI 95%: 1.03 -2.38) at calprotectin between 100 -200 ng/ml to HR 2.02 (CI 95%: 1.27-3.19) at calprotectin >200 ng/ml. P-calprotectin could be a useful marker of all-cause mortality in patients suffering from moderate to very severe COPD. [ABSTRACT FROM AUTHOR]

Circulating interleukin (IL)-18 is elevated in obesity, but paradoxically causes hypophagia. We hypothesized that IL-18 may attenuate high-fat diet (HFD)-induced insulin resistance by activating AMP-activated protein kinase (AMPK). We studied mice with a global deletion of the α-isoform of the IL-18 receptor (IL-18R-/-) fed a standard chow or HFD. We next performed gain-of-function experiments in skeletal muscle, in vitro, ex vivo, and in vivo. We show that IL-18 is implicated in metabolic homeostasis, inflammation, and insulin resistance via mechanisms involving the activation of AMPK in skeletal muscle. IL-18R-/- mice display increased weight gain, ectopic lipid deposition, inflammation, and reduced AMPK signaling in skeletal muscle. Treating myotubes or skeletal muscle strips with IL-18 activated AMPK and increased fat oxidation. Moreover, in vivo electroporation of IL-18 into skeletal muscle activated AMPK and concomitantly inhibited HFD-induced weight gain. In summary, IL-18 enhances AMPK signaling and lipid oxidation in skeletal muscle implicating IL-18 in metabolic homeostasis. [ABSTRACT FROM AUTHOR]

The article presents a study on the effects of antioxidant supplementation particularly vitamin C and E supplementation to endurance athletes in the U.S. It says that vitamin supplementation for physical exercise is associated with reactive oxygen and nitrogen species (RONS) production, which may cause cell damage. Even so, RONS are said to act as important signals for redox state and transcription factors, which may promote training adaptation. Meanwhile, it cites the use of double-blinded placebo-controlled design for the allocation of supplements to participants and a normal distribution for data analysis. Results showed that the ingestion of vitamin C and E to individuals does not alter endurance training adaptation.

The protein tyrosine phosphatases (PTPs) are now recognized as critical regulators of signal transduction under normal and pathophysiological conditions. In this analysis we have explored the sequence of the human genome to define the composition of the PTP family. Using public and proprietary sequence databases, we discovered one novel human PTP gene and defined chromosomal loci and exon structure of the additional 37 genes encoding known PTP transcripts. Direct orthologs were present in the mouse genome for all 38 human PTP genes. In addition, we identified 12 PTP pseudogenes unique to humans that have probably contaminated previous bioinformatics analysis of this gene family. PCR amplification and transcript sequencing indicate that some PTP pseudogenes are expressed, but their function (if any) is unknown. Furthermore, we analyzed the enhanced diversity generated by alternative splicing and provide predicted amino acid sequences for four human PTPs that are currently defined by fragments only. Finally, we correlated each PTP locus with genetic disease markers and identified 4 PTPs that map to known susceptibility loci for type 2 diabetes and 19 PTPs that map to regions frequently deleted in human cancers. We have made our analysis available at http://ptp.cshl.edu or http://science.novonordisk.com/ptp and we hope this resource will facilitate the functional characterization of these key enzymes.--Andersen, J. N., Jansen, P. G., Echwald, S. M., Mortensen, O. H., Fukada, T., Del Vecchio, R., Tonks, N. K., Møller, N. P. H. A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage. [ABSTRACT FROM AUTHOR]