Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α, and interleukin-6. Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1β and BMD at all sites. Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. Conclusions These findings may have therapeutic implications for enhancing bone density in these patients.     

Predictive value and limitations of animal models for human transplantation: do we need more models for facial transplantation?

Animal models have traditionally provided the basis for preliminary investigation of new techniques prior to trials taking place in human subjects. The timing of when to proceed with human trials is difficult, as the accuracy of preclinical models can only be determined with hindsight. This review outlines the progression from transplantation in animal models to man. Now that many transplant procedures are well established, it is possible to assess the predictive value and limitations of animal models. These results are of great importance in the current debate about composite tissue allotransplantation (CTA) and in particular facial transplantation. This progression of CTA from animal models to man is outlined and compared with early renal, cardiac, and liver transplants. There is some evidence to suggest that animal models may have been misleading in CTA and that this has effectively delayed the transition to humans. The role for animal models in facial transplantation, which is currently making the step to clinical trials, is discussed.     

Proceedings of the 2006 annual meeting of the Fetal Alcohol Spectrum Disorders Study Group.

This article describes the proceedings of the 2006 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG), which was held in Baltimore, Maryland on June 24, 2006. The meeting was held in conjunction with the annual meeting of the Research Society on Alcoholism and was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism. The 2005-2006 FASDSG officers, Daniel J. Bonthius (President), Heather Carmichael Olson (Vice-President), and Jennifer Thomas (Secretary-Treasurer), organized the meeting. Nationally prominent speakers delivered plenary lectures on topics of newborn screening, ethics, and neuroscience. Selected members of the FASDSG provided brief scientific data (FASt) reports, describing new research findings. Representatives from national agencies involved in fetal alcohol syndrome (FAS) research, treatment, and prevention provided updates regarding priorities, funding, and agency activities. Presentations were also made by the 2006 Student Merit Award recipient and by the 2006 Rosett Award recipient. The meeting served as a forum for clinicians, neuroscientists, psychologists, social scientists, and other professionals to discuss recent advances in FAS research and to identify the most important gaps in the understanding of alcohol-induced teratology.     

Genetic linkage analysis of pulmonary fibrotic response to silica in mice.

Inter-individual variations in the development of silicosis, even within the same environments, have been reported, which suggest the contribution of genetic factors in silicosis aetiology. The aim of the present study was to determine whether there is any significant genetic influence on the development of silicosis. Furthermore, which genetic loci are responsible for the pulmonary response to silica exposure? Eight strains of inbred mice were used to examine the genetic influence on the lung fibrotic response to silica exposure. After intercross-breeding between the most susceptible and most resistant strains, a genome-wide linkage analysis of quantitative trait loci (QTL) was performed. Hydroxyproline was applied as an index, and genotypes of 167 marker genes were analysed by fragment analysis using a capillary-type sequencer. There was significant inter-strain difference in the mean concentration of hydroxyproline contents among the eight strains of mice. Breeding studies were conducted between the most susceptible, C57BL/6J, and the most resistant strain, CBA/J. A genome-wide linkage analysis of silica-exposed intercrossed cohorts identified significant QTL on chromosome 4 and suggestive QTL on chromosomes 3 and 18. The present study demonstrates that genetic factors may play a significant role in fibrotic-lung responses to silica; one significant and two suggestive quantitative trait loci were identified.