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Systemic inflammation often leads to complications in critically ill patients. Activation of the receptor for advanced glycation end-products (RAGE) generates inflammatory cytokines, proteases, and oxidative stress and may link inflammation to subsequent organ damage. Furthermore, hyperglycemia-induced oxidative stress increases RAGE ligands and RAGE(More)
CONTEXT Responses to critical illness, such as excessive inflammation and hyperglycemia, may trigger detrimental chain reactions that damage cellular proteins and organelles. Such responses to illness contribute to the risk of (nonresolving) multiple organ dysfunction and adverse outcome. OBJECTIVE We studied autophagy as a bulk degradation pathway able(More)
OBJECTIVE Muscle weakness contributes to prolonged rehabilitation and adverse outcome of critically ill patients. Distinction between a neurogenic and/or myogenic underlying problem is difficult using routine diagnostic tools. Preferential loss of myosin has been suggested to point to a myogenic component. We evaluated markers of muscle atrophy and(More)
OBJECTIVE To study activation of intracellular pathways depending on nuclear factor kappa B (NFkappaB) and mitogen activated kinases (MAPK) in the synovium of patients with psoriatic arthritis before and after treatment with etanercept. METHODS Synovial biopsies were obtained by needle arthroscopy of the knee in 9 patients with active psoriatic arthritis(More)
OBJECTIVE Ligands and antagonists of the WNT pathway are linked to osteoporosis and osteoarthritis. In particular, polymorphisms in the FRZB gene, a secreted WNT antagonist, have been associated with osteoarthritis. The aim of this study was to examine cartilage and bone in Frzb(-/-) mice. METHODS The Frzb gene in mice was inactivated using a Cre/loxP(More)
Joint ankylosis is a major cause of disability in the human spondyloarthropathies. Here we report that this process partially recapitulates embryonic endochondral bone formation in a spontaneous model of arthritis in DBA/1 mice. Bone morphogenetic protein (BMP) signaling appears to be a key molecular pathway involved in this pathological cascade. Systemic(More)
BACKGROUND Patients who are critically ill can develop so-called intensive-care unit acquired weakness, which delays rehabilitation. Reduced muscle mass, quality, or both might have a role. The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) trial (registered with ClinicalTrials.gov, number NCT00512122)(More)
OBJECTIVE To examine the expression, regulation, and potential roles of bone morphogenetic proteins (BMPs) in arthritic synovium. METHODS Expression of BMPs in arthritic synovium from patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) and in noninflamed synovium from patients undergoing diagnostic or therapeutic arthroscopies was studied(More)
OBJECTIVE To study the relationship between inflammation and remodeling by inhibiting tumor necrosis factor alpha (TNFalpha) in male DBA/1 mice with spontaneous arthritis, a model of spondylarthritis (SpA). METHODS TNFalpha was inhibited using etanercept, a soluble TNF receptor. The efficacy of the dose used (25 micro g/mouse) was confirmed in methylated(More)
BACKGROUND Fibroblast-like synovial cells (FLS) can be cultured and expanded in vitro in monolayer. Little is known about the growth characteristics of FLS derived from different patients. OBJECTIVE To study FLS cultures, with particular attention to differences in growth rate of FLS from patients with rheumatoid arthritis (RA) and from other arthritic(More)