in-alone arm. Furthermore, the relatively low baseline Effects of L-Glutamine on Glycaemia and Safety in Diabetes HbA1c and short study duration may have limited the magnitude of change in outcome measures. In conclusion, daily glutamine administration for 4 weeks decreased HbA1c, irrespective of sitagliptin treatment in wellcontrolled type 2 diabetes patients treated with metformin. Glutamine administration also resulted in an apparent plasma volume expansion in this population and requires further study. Zirconium is one of the more common trace elements present PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19682730 in the environment. It is a metallic element with a valency of 4 that is normally present in human bone and tissues at a trace level in the range 220 mg/kg body weight with an estimated average daily intake in humans of 3.5 mg. Toxicity of Zr has been assessed as low to PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1968231 moderate in animals. Zr containing materials, predominantly as the stable and biologically inert zirconium oxide and metal alloys, have been widely used in dental applications and as coatings for 1 / 17 Zirconium Promotes Osteoblast Differentiation Competing Interests: The authors have declared that no competing SKI-II supplier interests exist. orthopaedic implants due to their contributions to biocompatibility, increased mechanical strength, and high corrosion resistance. Recently we have developed a calcium silicate-based ceramic, baghdadite incorporating Zr which can be released as Zr ions into aqueous media. This ceramic was more labile than the ZrO2 and has been shown to release Zr into solutions simulating body fluids at concentrations in the range 10100 M. This ceramic when fabricated as a porous scaffold, has been shown to have excellent osteogenic bioactivity in vitro and in vivo when compared to calcium silicate ceramics. This ceramic material has been tested in a critical sized bone defect model in the rabbit and appears to be superior in promoting osteogenesis than the currently used clinical implant materials containing calcium triphosphate and hydroxyapatite. We further demonstrated that Baghdadite scaffolds can modulate the crosstalk between adipose stem cells and primary human osteoblasts to promote osteogenic gene expression in both ASCs and HOBs in an indirect co-culture system. However the mechanism for this enhanced bioactivity has not been identified, and, in particular, the in vitro effects of Zr ions on human osteoblasts have not previously been studied. Review of the literature indicates an absence of studies evaluating the effects of Zr ions in cells of the osteoblast lineage. There has been one limited study reported in the literature examining the in vitro toxicity of Zr on the osteoblast-like cell line MG63 which showed cell toxicity in the millimolar concentration range but which did not investigate the effects of Zr ions on the proliferation and differentiation of these cells at lower more clinically relevant concentrations. The response of osteoblast-like cell lines and human osteoblasts have been 
assessed when grown on Zr containing alloys and ceramics but in none of these is it possible to differentiate surface morphology effects and the influence of other material components from those of Zr itself. Various trace elements have been found to have activity on bone cells. Strontium and fluoride ions have each been shown to have osteogenic properties for in vitro osteoblast cell cultures and when administered systemically, and gallium has been found to inhibit the activity of osteoclasts and in
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