Blood Thiol Redox State in Chronic Kidney Disease

Thiols (sulfhydryl groups) are effective antioxidants that can preserve the correct structure of proteins, and can protect cells and tissues from damage induced by oxidative stress. Abnormal levels of thiols have been measured in the blood of patients with moderate-to-severe chronic kidney disease (CKD) compared to healthy subjects, as well as in end-stage renal disease (ESRD) patients on haemodialysis or peritoneal dialysis. The levels of protein thiols (a measure of the endogenous antioxidant capacity inversely related to protein oxidation) and S-thiolated proteins (mixed disulphides of protein thiols and low molecular mass thiols), and the protein thiolation index (the molar ratio of the S-thiolated proteins to free protein thiols in plasma) have been investigated in the plasma or red blood cells of CKD and ESRD patients as possible biomarkers of oxidative stress. This type of minimally invasive analysis provides valuable information on the redox status of the less-easily accessible tissues and organs, and of the whole organism. This review provides an overview of reversible modifications in protein thiols in the setting of CKD and renal replacement therapy. The evidence suggests that protein thiols, S-thiolated proteins, and the protein thiolation index are promising biomarkers of reversible oxidative stress that could be included in the routine monitoring of CKD and ESRD patients.     

Experimental Evaluation of Thermal Properties of Grouting Materials

This study is aimed at the thermal analysis of sealant mortar （usually a mixtures of bentonite and cemem with addition of sand） used in geothermal cooling and heating. In particular, thermal conductivity and diffusivity measurements were performed on differem sealant mixtures by using Hot Disk thermal constants analyzer in order to identify the interesting thermal properties of grouting materials. The grouting materials that we considered are of porous nature and, if used in the presence of groundwater, have different levels of imbibitions. It is important to know the thermal behavior of these materials at different water content. A first set of measurements was performed on a not-tinted material at room temperature; then the samples were led to saturation conditions by contact capillary imbibitions with a cotton wool layer moistened in water. The determination of thermal conductivity in these test conditions appears to be critical compared to the measuremems on non-timed sample. The thermal conductivity tests have revealed how the thermal behavior of the samples analyzed is essentially determined by the density and water content of the material： in fact, the thermal conductivity increases of two to three times the value of the not-tinted material.     

Towards the development of technical specifications for the production of lithium–lead alloys for the ITER HCLL TMB

The ITER and DEMO projects are developing new Test Blanket Modules (TBM), where the Pb–Li alloy plays a key role in the new commercial fusion reactors functionality. The Breeding Blanket (BB) has to perform several functions which are essential for the reactor operation. The HCLL TBM is one of the Breeding Blanket concepts to be tested in ITER. It is cooled by He and uses the eutectic liquid metal LLE (Lithium–Lead Eutectic) as breeder material (enriched at 90% in ⁶Li).Pb–Li eutectic alloy has no known uses outside of fusion technology, so the available databases of this material are currently incomplete. It is very important, within the material specifications, to have a complete characterization in order to define their chemical and physical properties, because any variation in the alloy composition has significant consequences in their behaviour, and therefore in their regenerative function inside the blanket.The chemical characterization methodology developed and presented in this paper (useful for both Pb–Li alloys as any Pb alloy) is a key tool that allows performing standard quality control procedures for base material and/or monitoring the alloy during the reactor operation. This report provides a procedure to perform a wide material chemical characterization, assessing the concentrations of major elements, as well as a review of trace level elements that can be found both in the eutectic alloy and in starting materials. In this determination plays an important role the ICP-MS technique because, as a highly sensitive technique, allows very low detection limits.     

Clearance of FGF‐23 during continuous renal replacement therapy

FGF‐23 is a 32 kDa protein that is a key regulator of phosphorus and vitamin D metabolism. Emerging evidence also demonstrates that FGF‐23 increases within 24 hours of acute kidney injury (AKI) and may be associated with adverse clinical outcomes. We conducted this study to evaluate FGF23 clearance during continuous veno‐venous hemofiltration (CVVH) in critically ill patients with AKI. We demonstrate that plasma clearance of FGF‐23 during CVVH is ～11 mL/min and the mean sieving coefficient is 0.27 ± 0.1. Future studies will need to clarify FGF‐23's role in adverse outcomes among AKI patients, and whether therapies aimed at reducing FGF‐23 levels may be beneficial.     

Grape,apple and pineapple juice characterisation and detection of mixtures

Several multivariate statistical methods (principal component, cluster, stepwise discriminant and multiple linear regression analysis) were applied to analytical data obtained by conventional methods and to analytical data for free amino acids, in an attempt to distinguish between grape, apple and pineapple juice. Analysis for methionine, proline, asparagine, arginine and glutamic acid made it possible to differentiate among the 34 samples of grape, apple and pineapple juices studied. Multiple linear regression analysis of computer-simulated mixtures of grape and apple juices made it possible to detect the proportion of each fruit within the blend.     

Inhibitors of branched-chain amino acid biosynthesis as potential antituberculosis agents

Previous studies have shown that rheumatoid arthritis aggregates within families. However, no formal genetic analysis of rheumatoid arthritis in pedigrees together with other autoimmune diseases has been reported. We hypothesized that there are genetic factors in common in rheumatoid arthritis and other autoimmune diseases. Results of odds-ratio regression and complex segregation analysis in a sample of 43 Caucasian pedigrees ascertained through a rheumatoid arthritis proband or matched control proband, revealed a very strong genetic influence on the occurrence of both rheumatoid arthritis and other autoimmune diseases. In an analysis of rheumatoid arthritis alone, only one inter-class measure, parent-sibling, resulted in positive evidence of aggregation. However, three inter-class measures (parent-sibling, sibling-offspring, and parent-offspring pairs) showed significant evidence of familial aggregation with odds-ratio regression analysis of rheumatoid arthritis together with all other autoimmune diseases. Segregation analysis of rheumatoid arthritis alone revealed that the mixed model, including both polygenic and major gene components, was the most parsimonious. Similarly, segregation analysis of rheumatoid arthritis together with other autoimmune diseases revealed that a mixed model fitted the data significantly better than either major gene or polygenic models. These results were consistent with a previous study which concluded that several genes, including one with a major effect, is responsible for rheumatoid arthritis in families. Our data showed that this conclusion also held when the phenotype was defined as rheumatoid arthritis and/or other autoimmune diseases, suggesting that several major autoimmune diseases result from pleiotropic effects of a single major gene on a polygenic background.     

Different Contribution of Monocyte- and Platelet-Derived Microvesicles to Endothelial Behavior

Several contributions of circulating microvesicles (MVs) to the endothelial dysfunction have been reported in the past; a head-to-head comparison of platelet- and monocyte–derived MVs has however never been performed. To this aim, we assessed the involvement of these MVs in vessel damage related processes, i.e., oxidative stress, inflammation, and leukocyte-endothelial adhesion. Platelets and monocytes isolated from healthy subjects (HS, n = 15) were stimulated with TRAP-6 and LPS to release MVs that were added to human vascular endothelial cell (hECV) culture to evaluate superoxide anion production, inflammatory markers (IL-6, TNFα, NF-κB mRNA expression), and hECV adhesiveness. The effects of the MVs-induced from HS were compared to those induced by MVs spontaneously released from cells of patients with ST-segment elevation myocardial infarction (STEMI, n = 7). MVs released by HS-activated cells triggered a threefold increase in oxidative burst in a concentration-dependent manner. Only MVs released from monocytes doubled IL-6, TNFα, and NF-κB mRNA expression and monocyte-endothelial adhesion. Interestingly, the effects of the MVs isolated from STEMI-monocytes were not superimposable to previous ones except for adhesion to hECV. Conversely, MVs released from STEMI-platelets sustained both redox state and inflammatory phenotype. These data provide evidence that MVs released from activated and/or pathologic platelets and monocytes differently affect endothelial behavior, highlighting platelet-MVs as causative factors of impaired endothelial function in the acute phase of STEMI.     

Tumor-Stroma Ratio and Programmed Cell Death Ligand 1 Expression in Preoperative Biopsy and Matched Laryngeal Carcinoma Surgical Specimen

Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical–pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical–pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS < 1 evaluated on surgical specimens was associated with a low TSR (stroma rich) on both biopsies and surgical specimens (p = 0.0143 and p = 0.0063). Low TSR showed a significant negative prognostic value when evaluated on both biopsies and surgical specimens (HR = 8.808, p = 0.0003 and HR = 11.207, p = 0.0002). CPS ≥ 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols.