High concentrations of dexamethasone suppresses the proliferation but not the differentiation of further maturation of human osteoblast precursor in vitro: relevance to glucocorticoid-induced osteoporosis

Objective. The use of glucocorticoids (GCs) in the treatment of RA is a frequent cause of bone loss. In vitro, however, this same class of steroids has been shown to promote the recruitment and/or maturation of primitive osteogenic precursors present in the colony forming unit-fibroblastic (CFU-F) fraction of human bone and marrow. In an effort to reconcile these conflicting observations, we investigated the effects of the synthetic GC dexamethasone (Dx) on parameters of growth and osteogenic differentiation in cultures of bone marrow stromal cells derived from a large cohort of adult human donors (n=30). Methods. Marrow suspensions were cultured in the absence and presence of Dx at concentrations between 10 pm and 1 µm. After 28 days we determined the number and diameter of colonies formed, the total number of cells, the surface expression of receptors for selected growth factors and extracellular matrix proteins and, based on the expression of the developmental markers alkaline phosphatase (AP) and the antigen recognized by the STRO-1 monoclonal antibody, the proportion of cells undergoing osteogenic differentiation and their extent of maturation. Results. At a physiologically equivalent concentration, Dx had no effect on the adhesion of CFU-F or on their subsequent proliferation, but did promote their osteogenic differentiation and further maturation. These effects were independent of changes in the expression of the receptors for fibroblast growth factors, insulin-like growth factor 1, nerve growth factor, platelet-derived growth factors and parathyroid hormone/parathyroid hormone-related protein, but were associated with changes in the number of cells expressing the 2 and 4, but not ß1, integrin subunits. At supraphysiological concentrations, the effects of Dx on the osteogenic recruitment and maturation of CFU-F and their progeny were maintained but at the expense of a decrease in cell number. Conclusions. A decrease in the proliferation of osteogenic precursors, but not in their differentiation or maturation, is likely to be a key factor in the genesis of GC-induced bone loss.

Numerical simulation of the charge balance in an EBIT

The electron beam ions traps (EBITs) are widely used to study highly charged ions (HCIs). In an EBIT, a high energy electron beam collides with atoms and ions to generate HCIs in the trap region. It is important to study the physics in the trap. The atomic processes, such as electron impact ionisation (EI), radiative recombination (RR), dielectronic recombination (DR) and charge exchange (CX), occur in the trap and numerical simulation can give some parameters for design, predict the composition and describe charge state evolution in an EBIT [Phys. Rev. A 43 (199 1) 4861]. We are presently developing a new code, which additionally includes a description of the overlaps between the ion clouds of the various charge-states. It has been written so that it can simulate experiments where various machine parameters (e.g. beam energy and current) can vary throughout the simulation and will be able to use cross- sections either based on scaling laws or derived from atomic structure calculations. An object-oriented method is used in developing the new software, which is an efficient way to organize and write code. (C) 2003 Elsevier Science B.V. All rights reserved.

Europeanization, Conditionality and Domestic Change: The Twinning Exercise and Administrative Reform in Romania

A key requirement of the countries of central and eastern Europe (CEECs) that wish to join the EU is that they develop the administrative capacity to implement effectively the acquis communautaire. The 'twinning' programme is designed to assist in this process. Drawing on experiences in Romania, and linking these to debates on Europeanization, this article argues that the success of twinning to date is related to the design of the programme, institutional fluidity and politicization within central administration, the individual agency and the reform commitment of those hosting twinning projects.