The Proinflammatory Environment in Potential Heart and Lung Donors: Prevalence and Impact of Donor Management and Hormonal Therapy

BACKGROUND: Brain stem death can elicit a potentially manipulable cardiotoxic proinflammatory cytokine response. We investigated the prevalence of this response, the impact of donor management with tri-iodothyronine (T3) and methylprednisolone (MP) administration, and the relationship of biomarkers to organ function and transplant suitability. METHODS: In a prospective randomized double-blinded factorially designed study of T3 and MP therapy, we measured serum levels of interleukin-1 and -6 (IL-1 and IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein, and procalcitonin (PCT) levels in 79 potential heart or lung donors. Measurements were performed before and after 4 hr of algorithm-based donor management to optimize cardiorespiratory function and +/-hormone treatment. Donors were assigned to receive T3, MP, both drugs, or placebo. RESULTS: Initial IL-1 was elevated in 16% donors, IL-6 in 100%, TNF-alpha in 28%, CRP in 98%, and PCT in 87%. Overall biomarker concentrations did not change between initial and later measurements and neither T3 nor MP effected any change. Both PCT (P =0.02) and TNF-alpha (P =0.044) levels were higher in donor hearts with marginal hemodynamics at initial assessment. Higher PCT levels were related to worse cardiac index and right and left ventricular ejection fractions and a PCT level more than 2 ng x mL(-1) may attenuate any improvement in cardiac index gained by donor management. No differences were observed between initially marginal and nonmarginal donor lungs. A PCT level less than or equal to 2 ng x mL(-1) but not other biomarkers predicted transplant suitability following management. CONCLUSIONS: There is high prevalence of a proinflammatory environment in the organ donor that is not affected by tri-iodothyronine or MP therapy. High PCT and TNF-alpha levels are associated with donor heart dysfunction. (C) 2009 Lippincott Williams & Wilkins, Inc.

Reluctant donors? The Europeanization of international development policies in the New Member States

The European Union (EU) played an instrumental role in re-starting the international development policies in central and eastern European Member States, but questions remain about how far this policy area has been Europeanized since accession. Focusing on the Czech Republic, Hungary, Poland and Slovakia, this article investigates why the new donors have been reluctant to adopt the EU's development acquis more fully. The article traces the socialization processes offered by the EU's development policy rule-making and subsequent national rule implementation. The conclusions reveal three reasons why socialization has been weak: perceptions among the new Member States on the procedural legitimacy of the development acquis; low domestic resonance with the development acquis; and inconsistencies in the activities of norm entrepreneurs. The article contributes to our understanding of development policy in the EU – particularly how decision-making takes place within the Council and its working groups post-enlargement.

The East-Central European new donors:mapping capacity building and remaining challenges

In the past decade, the East-Central European countries were provided significant external capacity building assistance to help their emergence as donors of foreign aid. This paper aims to map these capacity development programmes and identify where they have helped and what challenges remain for the new donors. The main conclusion is that although capacity building has been instrumental in building organisational structures, working procedures and training staff, deeper underlying problems such as low levels of financing, lacking political will, the need for visibility and low staff numbers continue to hinder the new international development policies. Copyright © 2013 John Wiley & Sons, Ltd.

Aid allocation of the emerging Central and Eastern European donors

This paper examines the main characteristics of the (re-)emerging foreign aid policies of the Visegrád countries (the Czech Republic, Hungary, Poland, Slovakia), concentrating on the allocation of their aid resources. I adopt an econometric approach, similar to the ones used in the literature, for analysing the aid allocation of the OECD DAC donors. Using this approach, I examine the various factors that influence aid allocation of the Visegrád countries, using data for the years between 2001 and 2008. The most important conclusion is that the amount of aid a partner country gets from the four emerging donors is not influenced by the level of poverty or the previous performance of the recipients (measured by the level of economic growth or the quality of institutions). The main determining factor seems to be geographic proximity, as countries in the Western Balkans and the Post-Soviet region receive much more aid from the Visegrád countries than other recipients. Historical ties (pre-1989 development relations) and international obligations in the cases of Afghanistan and Iraq are also found to be significant explanatory factors. This allocation is in line with the foreign political and economic interests of these new donors. Although there are clear similarities between the four donors, this paper also identifies some individual country characteristics.

Characterization of human mesenchymal stem cells from multiple donors and the implications for large scale bioprocess development

Cell-based therapies have the potential to contribute to global healthcare, whereby the use of living cells and tissues can be used as medicinal therapies. Despite this potential, many challenges remain before the full value of this emerging field can be realized. The characterization of input material for cell-based therapy bioprocesses from multiple donors is necessary to identify and understand the potential implications of input variation on process development. In this work, we have characterized bone marrow derived human mesenchymal stem cells (BM-hMSCs) from multiple donors and discussed the implications of the measurable input variation on the development of autologous and allogeneic cell-based therapy manufacturing processes. The range of cumulative population doublings across the five BM-hMSC lines over 30 days of culture was 5.93, with an 18.2% range in colony forming efficiency at the end of the culture process and a 55.1% difference in the production of interleukin-6 between these cell lines. It has been demonstrated that this variation results in a range in the process time between these donor hMSC lines for a hypothetical product of over 13 days, creating potential batch timing issues when manufacturing products from multiple patients. All BM-hMSC donor lines demonstrated conformity to the ISCT criteria but showed a difference in cell morphology. Metabolite analysis showed that hMSCs from the different donors have a range in glucose consumption of 26.98 pmol cell−1 day−1, Lactate production of 29.45 pmol cell−1 day−1 and ammonium production of 1.35 pmol cell−1 day−1, demonstrating the extent of donor variability throughout the expansion process. Measuring informative product attributes during process development will facilitate progress towards consistent manufacturing processes, a critical step in the translation cell-based therapies.