First Report of Circulating MicroRNAs in Tumour Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)

Tumor necrosis factor-receptor associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder characterized by recurrent episodes of long-lasting fever and inflammation in different regions of the body, such as the musculo-skeletal system, skin, gastrointestinal tract, serosal membranes and eye. Our aims were to evaluate circulating microRNAs (miRNAs) levels in patients with TRAPS, in comparison to controls without inflammatory diseases, and to correlate their levels with parameters of disease activity and/or disease severity. Expression levels of circulating miRNAs were measured by Agilent microarrays in 29 serum samples from 15 TRAPS patients carrying mutations known to be associated with high disease penetrance and from 8 controls without inflammatory diseases. Differentially expressed and clinically relevant miRNAs were detected using GeneSpring GX software. We identified a 6 miRNAs signature able to discriminate TRAPS from controls. Moreover, 4 miRNAs were differentially expressed between patients treated with the interleukin (IL)-1 receptor antagonist, anakinra, and untreated patients. Of these, miR-92a-3p and miR-150-3p expression was found to be significantly reduced in untreated patients, while their expression levels were similar to controls in samples obtained during anakinra treatment. MiR-92b levels were inversely correlated with the number of fever attacks/year during the 1st year from the index attack of TRAPS, while miR-377-5p levels were positively correlated with serum amyloid A (SAA) circulating levels. Our data suggest that serum miRNA levels show a baseline pattern in TRAPS, and may serve as potential markers of response to therapeutic intervention

Human Apolipoprotein A-I-Derived Amyloid: Its Association with Atherosclerosis

Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits of nonvariant protein in atherosclerotic arteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this work we investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated with chronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pH promotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring protein deposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the protein give rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it may produce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated to atherogenesis

Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus

Effect of the photo-activation method on polymerization shrinkage of restorative composites

This study measured the gap that resulted from polymerization shrinkage of seven restorative resin composites after curing by three different methods. Contraction behavior, according to the specimen region, was also characterized. The materials used for this study were Alert (Jeneric/Pentron, Wallingford, CT 06492, USA), Surefil (Dentsply Caulk Milford, DE 19963, USA), P60 (3M Dental Products, St Paul, MN 55144, USA), Z250 (3M), Z100 (3M), Definite (Degussa-Huls, Hanau, Germany) and Flow-it (Jeneric/Pentron). The composite was placed in a circular brass mold 7 mm in diameter and 2 mm in height. Photo-activation was performed by a) continuous light (500 mW/cm(2)) for 40 seconds; b) stepped light with low intensity (150 mW/cm(2)) for 10 seconds and high intensity (500 mW/cm(2)) for 30 seconds and c) intermittent light (450 mW/cm(2)) for 60 seconds. The top and bottom surfaces were then polished and after 24 +/- 1 hours, the contraction gap was measured by SEM at variable pressure (LEO 435 VP, Cambridge, England). Results were analyzed by ANOVA and the means compared by Tukey's test (5%). The results demonstrated 1) the continuous light method presented the greatest gap values (15.88 mum), while the other methods demonstrated lower polymerization shrinkage values (stepped light, 13.26 mum; intermittent light, 12.79 mum); 2) restorative composites shrunk more at the bottom surface (15.84 mum) than at the top surface (12.11 mum) and (3) the composites Alert (12.02 mum), Surefil (11.86 mum), Z250 (10.81 mum) and P60 (10.17 mum) presented the least contraction gaps, followed by Z100 (15.84 mum) and Definite (14.06 mum) and finally Flow-it (23.09 mum) low viscosity composite, which had the greatest mean value.27219219

Monomer conversion at different dental composite depths using six light-curing methods

This study used infrared spectroscopy to compare the degree of conversion (DC) of Z250 resin composite at different depths, using a variety of light-curing sources. Photo-activation was performed with: plasma arc (PAC) light, a blue light emitting diode (LED) and four different exposure scenarios using quartz-tungsten-halogen (QTH) light. Cured composite cylinders were transversally cut into 300 pm-thick slices corresponding to surface, 1-5 mm depths. Each disc was finely pulverized, incorporated into KBr pellets, and analyzed by FTIR. Results demonstrated that for the surface and depths of 1 and 2 min, conversion values did not differ significantly between lights or exposure treatments. At 3 and 4 mm depths, the LED source showed significantly higher DC than did the PAC light. All QTH methods were not significantly different to either LED or PAC. At 5 mm, there was no significant difference in DC between methods, except that PAC was not able to cure the composite. (C) 2006 Elsevier Ltd. All rights reserved.25328228