The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

R apid initiation of a primary antigen-specific T cell immune response depends on the coordinated and efficient interaction between antigen-presenting dendritic cells (DC) and naive T cells. The chemokine receptor CCR7 and its homeostatic ligands CCL19 and CCL21 are pivotal for recirculation of both cell types into secondary lymphoid organs (SLO) (1). In particular, homing of CCR7-positive antigen-loaded mature DC into secondary lymphoid tissues occurs along a chemoattractant gradient of CCL19 or CCL21. DC that migrate within secondary lymphoid tissues spontaneously express CCL19 itself (2). Both chemokines also attract CCR7-positive naive and central memory T cells that support their colocalization with DC. Co-localized T cells encounter DC that are searching for a stimulating antigen within this specific microenvironment, the first step to initiate an immune response. In CCR7 genedeficient mice (CCR7 Ϫ/Ϫ ) or in the ligand-deficient mice (plt Ϫ/Ϫ ), the ability to initiate and generate a T H 1/T H 2 immune response, memory, or tolerance is severely limited (3-6). Targeting CCL19 or CCL21 might modulate immune responses in a clinically useful manner (7-9). To extend the in vivo half-life of the chemokine, we fused CCL19 to the Fc part of IgG1 and tested whether this CCL19-IgG is applicable as a therapeutic tool to interfere with CCR7-mediated recirculation. We detected an immunosuppressive effect mediated by CCL19-IgG in different murine models, including delayed-type hypersensitivity (DTH) and two different models of allograft transplantation.In this study we show, that in contrast to only limited prolongation of graft survival in transplantation models that were performed in CCR7-deficient mice (10,11), application of CCL19-IgG was able to provide a marked prolongation of both kidney and heart graft survival. The mechanisms involved include disturbed homing of T cells and DC into SLO as well as disturbed co-localization and consequently an impaired response of T cell priming, so the alterations of immune cell trafficking that are induced by CCL19-IgG are similar to the effects described for CCR7 deficiency. However, the discrepancy between our approach and knockout models show that, when interfering with CCR7 in an intact environment, there might be additive effects to those induced by the genetic knockout. To our knowledge, this is the first study to demonstrate a clinically applicable tool to target CCR7-mediated cell trafficking for immunosuppression after solid-organ transplantation.

CCR7 and its ligands, CCL19 and CCL21, are responsible for directing the migration of T cells and dendritic cells into lymph nodes, where these cells play an important role in the initiation of the immune response. Recently, we have shown that systemic application of CCL19-IgG is able to inhibit the colocalization of T cells and dendritic cells within secondary lymphoid organs, resulting in pronounced immunosuppression with reduced allograft rejection after organ transplantation. In this study, we demonstrate that the application of sustained high concentrations of either soluble or immobilized CCL19 and CCL21 elicits an inhibitory program in T cells. We show that these ligands specifically interfere with cell proliferation and IL-2 secretion of CCR7+ cells. This could be demonstrated for human and murine T cells and was valid for both CD4+ and CD8+ T cells. In contrast, CCL19 had no inhibitory effect on T cells from CCR7 knockout mice, but CCR7−/− T cells showed a proliferative response upon TCR-stimulation similar to that of CCL19-treated wild-type cells. Furthermore, the inhibition of proliferation is associated with delayed degradation of the cyclin-dependent kinase (CDK) inhibitor p27Kip1 and the down-regulation of CDK1. This shows that CCR7 signaling is linked to cell cycle control and that sustained engagement of CCR7, either by high concentrations of soluble ligands or by high density of immobilized ligands, is capable of inducing cell cycle arrest in TCR-stimulated cells. Thus, CCR7, a chemokine receptor that has been demonstrated to play an essential role during activation of the immune response, is also competent to directly inhibit T cell proliferation.

Background Dialyzers shall be designed to efficiently eliminate uremic toxins during a dialysis treatment, given that the accumulation of small and middle molecular weight uremic solutes is associated with increased mortality risk of patients with end-stage renal disease. In the present study we investigated the novel FX CorAL dialyzer with a modified membrane surface for the performance during online-hemodiafiltration in a clinical setting. Methods comPERFORM was a prospective, open, controlled, multi-centric, interventional, cross-over study with randomized treatment sequences. It randomized stable patients receiving regular post-dilution online hemodiafiltration (HDF) to FX CorAL 600 (Fresenius Medical Care Deutschland GmbH), xevonta Hi 15 (B. Braun), and ELISIO 150H (Nipro), each for one week. The primary outcome was β2-microglobulin removal rate (ß2-m RR) during online-HDF. Secondary endpoints were RR and/or clearance of ß2-m and other molecules. Albumin removal over time was an exploratory endpoint. Non-inferiority and superiority of FX CorAL 600 vs. competitors were tested. Results 52 patients were included and analyzed. FX CorAL 600 showed the highest ß2-m RR (75.47%), followed by xevonta Hi 15 (74.01%) and ELISIO 150H (72.70%). Superiority to its competitors was statistically significant (P = 0.0216 and P < 0.0001, respectively). Secondary endpoints related to middle molecules affirmed these results. FX CorAL 600 demonstrated the lowest albumin removal up to 60 min, and its sieving properties changed less over time than with competitors. Conclusions FX CorAL 600 efficiently removed middle and small molecules and was superior to the two comparators in ß2-m RR. Albumin sieving kinetics point to a reduced formation of a secondary membrane.

Evidence accumulates that in clinically relevant cell death, both the intrinsic and extrinsic apoptotic pathway synergistically contribute to organ failure. In search for an inhibitor of apoptosis that provides effective blockage of these pathways, we analyzed viral proteins that evolved to protect the infected host cells. In particular, the cowpox virus protein crmA has been demonstrated to be capable of blocking key caspases of both pro-apoptotic pathways. To deliver crmA into eukaryotic cells, we fused the TAT protein transduction domain of HIV to the N terminus of crmA. In vitro, the TAT-crmA fusion protein was efficiently translocated into target cells and inhibited apoptosis mediated through caspase-8, caspase-9, and caspase-3 after stimulation with ␣-Fas, etoposide, doxorubicin, or staurosporine. The extrinsic apoptotic pathway was investigated following ␣-Fas stimulation. In vivo 90% of TAT-crmA-treated animals survived an otherwise lethal dose of ␣-Fas and showed protection from Fas-induced organ failure. To examine the intrinsic apoptotic pathway, we investigated the survival of mice treated with an otherwise lethal dose of doxorubicin. Whereas all control mice died within 31 days, 40% of mice that concomitantly received intraperitoneal injections of TAT-crmA survived. To test the ability to comprehensively block both the intrinsic and extrinsic apoptotic pathway in a clinically relevant setting, we employed a murine cardiac ischemia-reperfusion model. TAT-crmA reduced infarction size by 40% and preserved left ventricular function. In summary, these results provide a proof of principle for the inhibition of apoptosis with TAT-crmA, which might provide a new treatment option for ischemia-reperfusion injuries.Apoptotic processes are centrally involved during organogenesis in complex organisms but may also cause organ failure in response to a variety of harmful stimuli. Certain infectious diseases, intoxications, or fulminant immune responses may trigger an overwhelming apoptotic response (1). Moreover, minimizing apoptotic organ failure due to ischemia-reperfusion injuries that occur during stroke or myocardial infarction remains a major challenge in clinical settings. Each year, ϳ1.5 million myocardial infarction cases are recorded in the United States. Myocardial infarction is the leading cause of death in both Europe and the United States. Therefore, transient blockage of apoptosis is of clinical importance to protect cardiac function and to save lives.Apoptosis is controlled by the extrinsic death receptor pathway and the intrinsic mitochondrial pathway. Notably, both pathways converge at caspase-3, leading to activation of other proteases. Caspases have more than 400 different substrates that interfere with transcription, translation, DNA cleavage, cytoskeleton assembly, and membrane trafficking. To prevent this "death by a thousand cuts," it is important to block caspases in both the intrinsic and extrinsic pathways as well as caspases involved in the execution process of apoptosis (2). The extrins...