European journal of clinical investigation
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Eur. J. Clin. Invest. · Jan 2012
Predominant role of obesity/insulin resistance in oxidative stress development.
Hyperlipidaemia, hyperglycaemia and hyperinsulinaemia, hallmarks of the postprandial state, have been also associated with increased oxidative stress and lipoprotein oxidation contributing to vascular injury and atherosclerosis. However, the specific links among metabolic disorders, postprandial state, insulin resistance and oxidative stress are still to be clarified. This study aimed at investigating the individual role played by obesity, insulin resistance and type 2 diabetes in the occurrence of fasting and postprandial oxidative stress. ⋯ Obesity and insulin resistance, more than type 2 diabetes, play the most relevant role in oxidative stress development. The correction of obesity and insulin resistance might be a useful strategy in counteracting systemic oxidative stress.
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Interleukin-10 is a pleiotropic cytokine, whose main function is limitation and ultimately termination of immune responses. This is especially true for environmental interfaces such as the gastrointestinal tract. IL-10 acts as a key mediator for maintaining gut homeostasis. IL-10 knockout mice are well established as a genetic model for inflammatory bowel disease (IBD), and sequence variants in the IL-10 locus contribute to ulcerative colitis (UC). ⋯ The discovery of inherited deregulations in the IL-10 signalling cascade is not only considered the missing link between IL-10 and intestinal homeostasis, but also demonstrates how findings made in animal models help explaining human disease.
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Eur. J. Clin. Invest. · Jan 2012
Adhesion molecules and high-sensitivity C-reactive protein levels in patients with sickle cell beta-thalassaemia.
The primary symptoms of sickle cell disease (SCD) arise from vaso-occlusive crises. The pathogenesis of these crises is complex phenomenon where endothelial activation and damage has a major role. Chronic inflammation also plays an important role in the pathophysiology of SCD. We aimed to investigate endothelial activation in Caucasian Greek patients with SCD by means of measuring adhesion molecules and markers of inflammation. ⋯ Our findings demonstrate the high degree of endothelial activation and damage seen in sickle cell patients even in steady-state condition, as well as the important chronic inflammation underlying the pathophysiology of this widespread disease.
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Eur. J. Clin. Invest. · Jan 2012
Profiling the expression of interleukin (IL)-28 and IL-28 receptor α in systemic lupus erythematosus patients.
Interleukin (IL)-28 is an interferon-λ-family member involved in immunity against viral infection and tumour. We here determined the expression profiles of IL-28 and IL-28 receptor α (IL-28RA) in patients with systemic lupus erythematosus (SLE) to evaluate the possibility that IL-28 is linked to the pathogenesis of SLE. ⋯ The expression of IL-28, a T-cell autocrine factor, is dysregulated in patients with SLE, supporting the possibility that IL-28 may contribute to some of the SLE pathogenesis.
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Eur. J. Clin. Invest. · Jan 2012
Phospholipase Cγ2 is required for basal but not oestrogen deficiency-induced bone resorption.
Osteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological bone loss during diseases including postmenopausal osteoporosis. Phospholipase Cγ2 (PLCγ2) is an important signalling molecule in diverse haematopoietic lineages. Here, we tested the role of PLCγ2 in basal and ovariectomy-induced bone resorption, as well as in in vitro osteoclast cultures using PLCγ2-deficient (PLCγ2(-/-) ) mice. ⋯ Our results indicate that PLCγ2 participates in bone resorption under basal conditions, likely because of its role in adhesion receptor signalling during osteoclast development. In contrast, PLCγ2 does not appear to play a major role in ovariectomy-induced bone loss. These results suggest that basal and oestrogen deficiency-induced bone resorption utilizes different signalling pathways and that PLCγ2 may not be a suitable therapeutic target in postmenopausal osteoporosis.