Hyperglycemia Activates Caspase-1 and TXNIP-Mediated IL-1β Transcription in Human Adipose Tissue

Contains fulltext : 96993.pdf (publisher's version ) (Closed access)OBJECTIVE: Obesity is characterized by elevated levels of proinflammatory cytokines, including interleukin (IL)-1beta, that contribute to the development of insulin resistance. In this study, we set out to investigate whether hyperglycemia drives IL-1beta production and caspase-1 activation in murine and human adipose tissue, thus inducing insulin resistance. RESEARCH DESIGN AND METHODS: ob/ob animals were used as a model to study obesity and hyperglycemia. Human adipose tissue fragments or adipocytes were cultured in medium containing normal or high glucose levels. Additionally, the role of thioredoxin interacting protein (TXNIP) in glucose-induced IL-1beta production was assessed. RESULTS: TXNIP and caspase-1 protein levels were more abundantly expressed in adipose tissue of hyperglycemic ob/ob animals as compared with wild-type mice. In human adipose tissue, high glucose resulted in a 10-fold upregulation of TXNIP gene expression levels (P < 0.01) and a 10% elevation of caspase-1 activity (P < 0.05), together with induction of IL-1beta transcription (twofold, P < 0.01) and a significant increase in IL-1beta secretion. TXNIP suppression in human adipocytes, either by a small interfering RNA approach or a peroxisome proliferator-activated receptor-gamma agonist, counteracted the effects of high glucose on bioactive IL-1 production (P < 0.01) mainly through a decrease in transcription levels paralleled by reduced intracellular pro-IL-1beta levels. CONCLUSIONS: High glucose activates caspase-1 in human and murine adipose tissue. Glucose-induced activation of TXNIP mediates IL-1beta mRNA expression levels and intracellular pro-IL-1beta accumulation in adipose tissue. The concerted actions lead to enhanced secretion of IL-1beta in adipose tissue that may contribute to the development of insulin resistance

The Effect of Aggressive Versus Conventional Lipid-lowering Therapy on Markers of Inflammatory and Oxidative Stress

Purpose Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention. It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins. We aimed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress. Materials and methods This was a multi-centre, double-blind, placebo-controlled trial. Patients with previous cardiovascular disease, who did not achieve low density lipoprotein (LDL) cholesterol levels <2.6 mmol/l on conventional statin therapy (simvastatin 40 mg) were randomized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks (aggressive treatment). Lipids, C-reactive protein, soluble cellular adhesion molecules, neopterin, von Willebrand Factor, and antibodies against oxidized LDL were measured at baseline and after 16 weeks. Results Lipid levels decreased significantly in the aggressive treatment group (LDL-C reduction 20.8%; P <0.001), whereas a slight increase was observed in the conventional group (LDL-C increase 3.7%; P = 0.037). A significant reduction in antibodies against oxidized LDL was seen in the aggressive (13.4%; P <0.001) and the conventional (26.8%; P <0.001) group, but there was no difference between groups (P = 0.25). Furthermore, no significant differences in change in other biomarkers was observed between both groups. Conclusions This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy

Hearing shapes of drums - mathematical and physical aspects of isospectrality

In a celebrated paper '"Can one hear the shape of a drum?"' M. Kac [Amer. Math. Monthly 73, 1 (1966)] asked his famous question about the existence of nonisometric billiards having the same spectrum of the Laplacian. This question was eventually answered positively in 1992 by the construction of noncongruent planar isospectral pairs. This review highlights mathematical and physical aspects of isospectrality.Comment: 42 pages, 60 figure

Bibliographie de l'histoire de Belgique : bibliografie van de geschiedenis van België. 1986

Van Eenoo R., Scufflaire Andrée, Bovesse J., Dumont M.-E., Hélin Etienne, Petit R., Van Derveeghde Denise, Prevenier Walter, Triaille-Closset C., Tits-Dieuaide M.-J., Vermeulen U., Gaus H., Witte Els, Lis Catharina, Cauchies J. M., Haesenne-Peremans N., Maréchal Griet, François Luc, Meyers W., Geirnaert Ν., De Wever B., Art J. Bibliographie de l'histoire de Belgique — Bibliografie van de geschiedenis van België. 1986. In: Revue belge de philologie et d'histoire, tome 66, fasc. 2, 1988. Histoire - Geschiedenis. pp. 329-430

Formation of stable uranium(VI) colloidal nanoparticles in conditions relevant to radioactive waste disposal

The favored pathway for disposal of higher activity radioactive wastes is via deep geological disposal. Many geological disposal facility designs include cement in their engineering design. Over the long term, interaction of groundwater with the cement and waste will form a plume of a hyperalkaline leachate (pH 10-13), and the behavior of radionuclides needs to be constrained under these extreme conditions to minimize the environmental hazard from the wastes. For uranium, a key component of many radioactive wastes, thermodynamic modeling predicts that, at high pH, U(VI) solubility will be very low (nM or lower) and controlled by equilibrium with solid phase alkali and alkaline-earth uranates. However, the formation of U(VI) colloids could potentially enhance the mobility of U(VI) under these conditions, and characterizing the potential for formation and medium-term stability of U(VI) colloids is important in underpinning our understanding of U behavior in waste disposal. Reflecting this, we applied conventional geochemical and microscopy techniques combined with synchrotron based in situ and ex situ X-ray techniques (small-angle X-ray scattering and X-ray adsorption spectroscopy (XAS)) to characterize colloidal U(VI) nanoparticles in a synthetic cement leachate (pH > 13) containing 4.2-252 μM U(VI). The results show that in cement leachates with 42 μM U(VI), colloids formed within hours and remained stable for several years. The colloids consisted of 1.5-1.8 nm nanoparticles with a proportion forming 20-60 nm aggregates. Using XAS and electron microscopy, we were able to determine that the colloidal nanoparticles had a clarkeite (sodium-uranate)-type crystallographic structure. The presented results have clear and hitherto unrecognized implications for the mobility of U(VI) in cementitious environments, in particular those associated with the geological disposal of nuclear waste