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Utrecht, Netherlands

Hollman D.A.A.,Netherlands Metabolomics Center | Milona A.,Netherlands Metabolomics Center | Van Erpecum K.J.,UMC Utrecht | Van Mil S.W.C.,Netherlands Metabolomics Center
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2012

The farnesoid X receptor (FXR) is a ligand-activated transcription factor belonging to the nuclear receptor (NR) superfamily. FXR plays an important role in positively regulating genes (transactivation) involved in bile acid homeostasis, fat and glucose metabolism. Recently, it has become clear that an additional important role for FXR consists of downregulating genes involved in inflammation. Because of this broad spectrum of regulated genes, therapeutically targeting FXR with full agonists will likely result in adverse side effects, in line with what is described for other NRs. It may therefore be necessary to develop selective FXR modulators. However, the molecular mechanisms that distinguish between FXR-mediated transactivation and transrepression are currently unknown. For other NRs, post-translational modifications such as SUMOylation and phosphorylation have been reported to be unique to either transactivation or transrepression. Here, we review current knowledge on post-translational regulation of FXR with respect to transactivation and transrepression. Ultimately, increased understanding of the different mechanisms of transactivation and transrepression of nuclear receptors will aid in the development of NR drugs with fewer side effects. © 2012 Elsevier B.V. Source


• The aim of this article is to provide guidance for the assessment of articles on randomised trials. This guide is intended for those who may want to apply the published results of randomised trials in everyday medical practice. • In order to be able to attribute the observed differences in health outcomes between treatment groups with due certainty to the treatment being evaluated, it is necessary that the groups are comparable at the start of the study, during the study, and at the end of the study, i.e. when measuring the outcomes. • In order to interpret the results of randomised trials and generalise these results to clinical practice, it is also necessary to consider the purpose of the study, the comparison that is made, the magnitude and direction of the observed effect, and to whom that effect applies. Source


Ledebo I.,Gambro | Blankestijn P.J.,UMC Utrecht
NDT Plus | Year: 2010

Haemodiafiltration (HDF) is the blood purification therapy of choice for those who want significant removal of uraemic solutes beyond the traditional range of small molecules. Combining diffusive and convective solute transport, a HDF treatment comprises the largest number of variables among blood purification therapies, and it is important to understand how they interact in order to optimize the therapy. This review discusses the parameters that determine the efficiency of HDF and how they can be controlled in the different forms of HDF and 'HDF-like' therapies practised today. The key to safe and effective HDF therapy is to have access to large volumes of high-quality fluids. Starting with ultrapure dialysis fluid, on-line preparation of a sterile, non-pyrogenic substitution solution can be made an integral part of the treatment, and we describe the necessary conditions for this. On-line HDF can provide the largest removal of the widest range of solutes among available dialysis therapies, and the potential clinical benefits of this are within practical reach for the increasing number of patients dialysed with high-flux membranes and ultrapure dialysis fluid. © The Author 2009. Published by Oxford University Press. Source


Koppen A.,UMC Utrecht | Koppen A.,Netherlands Metabolomics Center | Kalkhoven E.,UMC Utrecht | Kalkhoven E.,Netherlands Metabolomics Center
FEBS Letters | Year: 2010

The development of adipose tissue is a process which involves the concerted cooperation of numerous transcription factors together with their coactivators and corepressors. The peroxisome proliferator-activated receptor γ (PPARγ) is considered to be one of the master regulators of adipocyte differentiation. The presence of two functionally distinct types of adipose tissue, white and brown (WAT and BAT), requires an even more complex regulation of adipose tissue development. In this review we will focus on the role of PPARγ coregulators in adipogenesis and especially on the role of PPARγ coregulators in white and brown adipose tissue. Specificity in coregulator function in WAT and BAT may form an additional level of regulation of adipose tissue development. © 2010 Federation of European Biochemical Societies. Source


De Borst G.J.,UMC Utrecht | Moll F.L.,UMC Utrecht
Journal of Endovascular Therapy | Year: 2012

At present, no widely accepted surgical options exist for treating chronic deep venous insufficiency (CDVI). Experimental efforts to improve catheter-based management for CDVI have shown disappointing results, hindering application of these techniques in the clinical arena. A review of the literature focusing on technical aspects of valve stent design was conducted. Eight experimental studies were scrutinized to derive data on (1) stent design and configuration; (2) valve design, composition, and configuration; (3) delivery system; (4) functional outcome; and (5) histology to provide a basis for the design of a new prosthetic venous valve. The analysis of available experimental data found that all prosthetic valve designs currently under development/testing rely on some type of a stent to act as a carrier or frame for valve attachment. Most valve models reviewed were for the most part implanted safely and accurately, with good short-term patency and competency. The most commonly reported adverse event was thrombosis, which limited durability. It is assumed that valve configuration determines long-term results after repair. Hence, the newly proposed valve design consisted of 2 stent rings without barbs to fix the valve in the host vein. Because a little reflux might actually benefit the patency of the valve, the valve cusp in the new design forms a billowing "sail" that does not completely open or close, which also prevents the valve cusp from sticking to the wall. This technology remains of great interest to the interventionist and all physicians who are involved in the care for patients with advanced chronic venous disease. Valve design remains a challenge, but promising new valve substitutes such as the one outlined here are under evaluation. © 2012 by the International Society of Endovascular Specialists. Source

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