Physical Activity, Depression and Quality of Life in COPD - Results from the CLARA II Study.

Background: Symptoms of depression, pain and limitations in physical activity may affect quality of life in COPD patients independent from their respiratory burden. We aimed to analyze the associations of these factors in outpatients with COPD in Austria in a stable phase of disease.

Methods: We conducted a national, cross-sectional study among patients with COPD.

Quality of Life and Limitations in Daily Life of Stable COPD Outpatients in a Real-World Setting in Austria - Results from the CLARA Project.

Background: COPD patients suffer from respiratory symptoms and limitations in daily life. We aimed to characterize the impact of disease on overall health, daily life, and perceived well-being in COPD outpatients.

Methods: We conducted a national, cross-sectional study among pulmonologists and general practitioners (GPs).

Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium.

Double-stranded DNA (dsDNA) constitutes a potent activator of innate immunity, given its ability to bind intracellular pattern recognition receptors during viral infections or sterile tissue damage. While effects of dsDNA in immune cells have been extensively studied, dsDNA signalling and its pathophysiological implications in non-immune cells, such as the vascular endothelium, remain poorly understood. The aim of this study was to characterize prothrombotic effects of dsDNA in vascular endothelial cells.

Arterial thrombosis in the context of HCV-associated vascular disease can be prevented by protein C.

Hepatitis C virus (HCV) infection is a major problem worldwide. HCV is not limited to liver disease but is frequently complicated by immune-mediated extrahepatic manifestations such as glomerulonephritis or vasculitis. A fatal complication of HCV-associated vascular disease is thrombosis.

BK virus infection activates the TNFα/TNF receptor system in Polyomavirus-associated nephropathy.

Polyomavirus-associated nephropathy due to BK virus infection (BKVAN) is recognized as an important cause of significant kidney transplant dysfunction often leading to renal graft loss. The activation of innate immune defense mechanisms during BKVAN is still poorly understood and an altered regulation of inflammatory mediators by resident kidney cells upon viral infection can be expected to contribute to the onset and progression of disease. TNFα interacting with its receptors, TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), is largely accepted to be involved in viral responses, exhibiting both proinflammatory and immunosuppressive effects.

LL37 inhibits the inflammatory endothelial response induced by viral or endogenous DNA.

In viral infection, morbidity and mortality often result from extrahepatic disease manifestations such as vasculitis. We hereby show that human microvascular endothelial cells express viral receptors of the innate immune system which are induced upon ligand engagement. Furthermore, stimulation of endothelial cells with the synthetic analog of viral DNA, poly (dA:dT), human DNA and hepatitis B virus-containing immunoprecipitates from a patient with polyarteritis nodosa induces an inflammatory response including the upregulation of adhesion molecules, which is mediated exclusively by TLR9 and involves an IRF3-dependent pathway.

Hepatitis C virus induced endothelial inflammatory response depends on the functional expression of TNFα receptor subtype 2.

In hepatitis C virus (HCV) infection, morbidity and mortality often result from extrahepatic disease manifestations. We provide evidence for a role of receptors of the innate immune system in virally induced inflammation of the endothelium in vitro and in vivo. Corresponding to the in vitro finding of an HCV-dependent induction of proinflammatory mediators in endothelial cells, mice treated with poly (I:C) exhibit a significant reduction in leukocyte rolling velocity, an increase in leukocyte adhesion to the vessel wall and an increased extravasation of leukocytes.

Prothrombotic effects of tumor necrosis factor alpha in vivo are amplified by the absence of TNF-alpha receptor subtype 1 and require TNF-alpha receptor subtype 2.

Introduction: Elevated serum levels of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) correlate with an increased risk for atherothrombotic events and TNFα is known to induce prothrombotic molecules in endothelial cells. Based on the preexisting evidence for the impact of TNFα in the pathogenesis of autoimmune disorders and their known association with an acquired hypercoagulability, we investigated the effects of TNFα and the role of the TNF receptor subtypes TNFR1 and TNFR2 for arteriolar thrombosis in vivo.

Methods: Arteriolar thrombosis and platelet-rolling in vivo were investigated in wildtype, TNFR1-/-, TNFR2-/- and TNFR1-/R2-/- C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model.

TNFα enhances TLR3-dependent effects on MMP-9 expression in human mesangial cells.

The role of MMPs (matrix metalloproteinases) in kidney diseases has been widely accepted, where they can regulate inflammatory response because of their effects on both recruitment and survival of inflammatory cells. TNFα (tumour necrosis factor α) has also been implicated in the pathogenesis of inflammatory kidney diseases, including forms of glomerulonephritis associated with viral diseases. Previously, we established the functional linkage between viral receptors of the innate immune system, the TLRs (Toll-like receptors) and control of MMP activity in human MC (mesangial cells).

Response of VEGF to activation of viral receptors and TNFα in human mesangial cells.

Vascular endothelial growth factor (VEGF) plays an important role in glomerular homeostasis as well as in the pathogenesis of kidney diseases as glomerulonephritis (GN) and diabetic nephropathy. Mesangial cells (MC), which are an integral part of the functional glomerular filtration barrier in that providing structural support, can behave like inflammatory cells and produce mediators as chemokines and growth factors; they are known to express viral receptors, with TLR3 having been attributed relevance in viral disease-associated GN. Experiments were performed on human MC in cell culture.

Sclerosing peritonitis: a rare but fatal complication of peritoneal inflammation.

Sclerosing peritonitis is a rare form of peritoneal inflammation with an often fatal outcome. The major risk factor of sclerosing peritonitis is peritoneal dialysis treatment but it can also occur following renal or liver transplantation or be associated with certain drug treatment. This article gives an overview of reasons and treatment options for sclerosing peritonitis and shows a summery of current literature about sclerosing peritonitis.

TLR3-dependent immune regulatory functions of human mesangial cells.

In glomerulonephritis, the migration of inflammatory cells into the glomerulus is an important step in disease initiation and progression. The viral receptor Toll-like receptor 3 (TLR3) is known to play a role in virus-associated glomerulonephritis. Based on this knowledge, this study aimed to define the effects of the TLR3 ligand polyriboinosinic:polyribocytidylic acid (poly(I:C)) on the expression of adhesion molecules and macrophage colony-stimulating factor (M-CSF) on resident glomerular cells.

Inhibition of TLR3-mediated proinflammatory effects by Alkylphosphocholines in human retinal pigment epithelial cells.

PURPOSE. To elucidate the role of Toll-like receptor 3 (TLR3) in the pathogenesis of age-related macular degeneration (AMD) and to investigate the effect of alkylphosphocholines (APCs) on the TLR3-mediated expression of cytokines and growth factors in human retinal pigment epithelial (RPE) cells. METHODS.

TLR3-dependent regulation of cytokines in human mesangial cells: a novel role for IP-10 and TNF-alpha in hepatitis C-associated glomerulonephritis.

In viral infections, disease manifestations and tissue damage often result primarily from immune cells infiltrating target organs on the basis of an ineffectual viral clearance with persistent antigenemia or an inappropriate immune response. Cell types and mediators defining these inflammatory processes are still inadequately understood. In hepatitis C virus-associated glomerulonephritis, analysis of interferon-γ-inducible protein (IP-10) as a chemokine centrally involved in early antiviral response and TNF-α known to balance proinflammatory and immunosuppressive effects in inflammation shows a significant upregulation of both IP-10 and TNF-α mediated specifically by the viral receptor Toll-like receptor 3 expressed on mesangial cells.

Synthetic double-stranded RNA stimulates the expression of interferon-inducible protein 10 in human mesothelial cells.

Interferon-inducible protein 10 (IP-10) is a chemokine playing an important role in the restriction of viral spread. A time- and dose-dependent increase in IP-10 is found upon activation of viral receptors expressed on mesothelial cells, which provides novel evidence for a link between viral infections and inflammation of serous membranes.

Interstitial nephritis and autoimmune pancreatitis: a case report.

Autoimmune pancreatitis is a rare form of pancreatitis characterized by responsiveness to steroid therapy and an often relapsing disease course. The mainstay of therapy is oral corticotherapy. Associations of interstitial nephritis with various autoimmune disorders have been described.

Cystatin C and creatinine as markers for radiocontrast-induced nephropathy in patients treated with N-acetylcysteine.

The beneficial effect of N-acetylcysteine (NAC) in the prevention of radiocontrast-induced nephropathy (RCIN) as well as the definition of an adequate surrogate parameter for the evaluation of the incidence of RCIN remain points of controversial discussion. Nearly all clinical studies used an increase in serum creatinine to define renal injury, although cystatin C is suggested to be superior to creatinine in estimating glomerular filtration rate (GFR). Furthermore, a recent study showed that in healthy volunteers, NAC leads to a decrease in serum creatinine without influencing serum cystatin C concentrations, implicating a possible overestimation of the protective effect of NAC on the incidence of RCIN.

Effect of activation of viral receptors on the gelatinases MMP-2 and MMP-9 in human mesothelial cells.

Background: Extracellular matrix (ECM) not only provides molecular and spatial information that influence cell proliferation, differentiation and apoptosis but also has the potential to bind and present or release cytokines and cytotactic factors. Synthesis and degradation of extracellular matrix components are balanced by matrix metalloproteinases (MMP) and their inhibitors. In the pericardium as well as in the pleural and peritoneal cavities a multitude of clinically relevant disease states ranging from inflammation to fibrosis and tumor invasion result from altered regulation of MMP activity and are known to be associated with viral disease.

Effect of dsRNA on mesangial cell synthesis of plasminogen activator inhibitor type 1 and tissue plasminogen activator.

Background/aims: Viral infections are a major problem worldwide and many of them are complicated by virally induced glomerulonephritides. Progression of kidney disease to renal failure is mainly attributed to the development of renal fibrosis characterized by the accumulation of extracellular matrix components in the mesangial cell compartment and the glomerular basement membrane. Plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) are major regulators of plasmin generation and play an important role in generation and degradation of glomerular extracellular matrix components.

Comparative promoter analysis allows de novo identification of specialized cell junction-associated proteins.

Shared transcription factor binding sites that are conserved in distance and orientation help control the expression of gene products that act together in the same biological context. New bioinformatics approaches allow the rapid characterization of shared promoter structures and can be used to find novel interacting molecules. Here, these principles are demonstrated by using molecules linked to the unique functional unit of the glomerular slit diaphragm.

Novel role of toll-like receptor 3 in hepatitis C-associated glomerulonephritis.

Hepatitis C virus (HCV) infection is frequently complicated by glomerulonephritis with immune complexes containing viral RNA. We examined the potential influence of Toll-like receptors (TLRs), specifically TLR3 recognition of viral dsRNA exemplified by polyriboinosinic:polyribocytidylic acid [poly(I:C) RNA]. Normal human kidney stained positive for TLR3 on mesangial cells (MCs), vascular smooth muscle cells, and collecting duct epithelium.

Sam68-like mammalian protein 2, identified by digital differential display as expressed by podocytes, is induced in proteinuria and involved in splice site selection of vascular endothelial growth factor.

Podocytes, the glomerular epithelial cells of the kidney, share important features with neuronal cells. In addition to phenotypical and functional similarities, a number of gene products have been found to be expressed exclusively or predominantly by both cell types. With the hypothesis of a common transcriptome shared by podocytes and neurons, digital differential display was used to identify novel podocyte-expressed gene products.

Functional consequences of integrin-linked kinase activation in podocyte damage.

Background: The delicate foot process architecture of glomerular podocytes critically depends on integrin mediated cell-glomerular basement membrane (GBM) interaction. Integrin signaling via the integrin-linked kinase (ILK) is activated in podocyte damage and associated with considerable podocyte phenotype alterations. ILK has been shown to regulate cell fate via nuclear interaction of beta-catenin with lymphoid enhancer factor (LEF-1) transcription factors.