250 research outputs found
Design choices and intervention techniques for repairing and strengthening of the Monza cathedral bell-tower
No full textThe fundamental design choices and of the selection of the most appropriate materials and techniques which have been made for strengthening the Monza cathedral bell-tower, based on investigation and structural assessment carried out prior to and during the design process are presented. The results of the experimental and numerical investigation will first be given in order to explain the reasons for the design choice
The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus
No full textA state of subclinical systemic inflammation is characteristically present in obesity/insulin resistance and type 2 diabetes mellitus (T2DM). The aim of the study was to develop an integrated measure of the circulating cytokines involved in the subclinical systemic inflammation and evaluate its relation with whole-body insulin sensitivity and glucose metabolism in T2DM. T2DM patients (n = 17, M/F 13/4, age = 55.0 ± 1.7 years, BMI = 33.5 ± 1.5 kg/m(2), HbA(1c) = 7.7 ± 0.3%) and normal glucose-tolerant (NGT) subjects (n = 15, M/F 7/8, age = 49.1 ± 2.5 years, BMI = 31.8 ± 1.2 kg/m(2), HbA(1c) = 5.6 ± 0.1%) were studied in a cross-sectional design. Whole-body insulin sensitivity was quantified by the euglycemic clamp. Beta-cell function [disposition index (DI)] was calculated using insulin and glucose values derived from an oral glucose tolerance test and the euglycemic clamp. Body fat mass was evaluated by dual-energy X-ray absorptiometry. Plasma cytokine [TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin] values were divided into quintiles. A score ranging from 0 (lowest quintile) to 4 (highest quintile) was assigned. The inflammatory score (IS) was the sum of each cytokine score from which adiponectin score was subtracted in each study subject. Inflammatory cytokine levels were all higher in T2DM. IS was higher in T2DM as compared to NGT (10.0 ± 1.1 vs. 4.8 ± 0.8; p < 0.001). IS positively correlated with fasting plasma glucose (r = 0.638, p < 0.001), 1-h plasma glucose (r = 0.483, p = 0.005), 2-h plasma glucose (r = 0.611, p < 0.001) and HbA1c (r = 0.469, p = 0.007). IS was inversely correlated with insulin sensitivity (r = -0.478, p = 0.006) and DI (r = -0.523, p = 0.002). IS did not correlate with BMI and body fat mass. IS was an independent predictor of fasting plasma glucose and had a high sensibility and sensitivity to predict insulin resistance (M/I < 4). A state of subclinical inflammation defined and quantifiable by inflammatory score including TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin is associated with both hyperglycemia and whole-body insulin resistance in T2DM
Interactions with retinol and retinoids of bovine cellular retinol-binding protein
No full textThe interactions with retinol and retinol analogs of bovine cellular retinol-binding protein (CRBP) have been investigated, by means of fluorescence titrations, to obtain more information on the structural features of retinoid that may be required for their interaction with the binding protein. An approximately stoichiometric binding of retinol to bovine CRBP (K'd approximately 2 nM) has been found in direct binding assays. Although retinal exhibited relatively high binding affinity to bovine CRBP (K'd approximately 30 nM), a large excess of the retinoid could not compete with retinol for the carrier protein. On the assumption that retinol and retinal interact with the same binding site, this result indicates that the above-mentioned apparent dissociation constant for retinol.CRBP may be an overestimate and that its value may be as low as 0.1 nM. The finding of an exceedingly tight binding of retinol to CRBP provides further support for the possible role of CRBP-bound retinol, rather than its uncomplexed labile form, as substrate of enzymes involved in the metabolism of the vitamin. The results of these and previous studies indicate that CRBP is particularly sensitive to modifications of the retinol hydroxyl end group. Axerophthene, a retinol analog bearing a hydrogen atom in place of the hydroxyl end group, and beta-ionone exhibit rather low binding affinities for CRBP (K'd approximately 0.2 microM and approximately 4 microM, respectively), suggesting that the hydroxyl group and isoprene tail moieties contribute substantially to the retinol-binding affinity and specificity. These findings are consistent with the indications emerging from the three-dimensional structure determination of retinol.CRBP [Cowan, S. W., Newcomer, M. E. & Jones, T. A. (1993) J. Mol. Biol. 230, 1225-1246]. Additionally, the bulky end groups of fenretinide and N-ethyl retinamide replacing the retinol hydroxyl group have been found to prevent retinoid binding to CRBP. The primary structure of bovine CRBP has been determined and is highly similar to the structures of both human and rat CRBP (97% and 95% identical, respectively)
INTERNAL-ROTATION AROUND SINGLE BONDS AND CONFORMATIONAL PREFERENCES IN HETEROCYCLIC-ANALOGS OF BENZYL METHYL SULFOXIDE STUDIED WITH NMR TECHNIQUES
No full textThe conformational equilibrium related to the internal rotation processes occurring in sulphoxides of the type ArCH2SOCH3 (where Ar=2-thienyl, 2-furyl, 2-pyridinyl and (3-methyl)2-pyridinyl rings) were studied with H-1 and C-13 NMR spectroscopy. Proton chemical shifts and long-range coupling constants (n)J(H, H) were obtained from the iterative analysis of the multiplets and were employed, together with C-13 chemical shifts, long-range (n)J(C, H) and relaxation parameters (NOE and non-selective T-1 values) to obtain stereochemical relationships between the protons present in these molecules. Conformational predictions at a qualitative level were also derived from total molecular energies calculated with the semi-empirical AM1/MNDO method as a function of internal coordinates. The different approaches converged to indicate that the heterocyclic rings adopt an average orientation similar to the perpendicular orientation of the phenyl ring in benzyl methyl sulphoxide and, as regards rotation around the CH2-S bond, the prevalent conformer shows that the methyl group is symmetrically oriented with respect to the methylenic protons, The barriers for internal rotation are rather low and the equilibrium between conformers is dependent on the medium properties. Attempts to obtain conformational results were performed for the molecule of omeprazole, an antiulcer drug which contains the ArCH2SO-R moiety (Ar and R are substituted 2-pyridinyl and 2-benzimidazolyl groups, respectively). With respect to the other compounds examined, the orientation of the Ar ring does not significantly differ and the benzimidazole ring seems to prefer an orientation stereochemically equivalent to that of the methyl group
Beneficial effects on anthropometric and metabolic parameters in overweight and obese boys after 1 year nutritional-behavioral intervention
No full textBackground and aims: The prevalence of obesity and the risk for metabolic, cardiovascular, and liver diseases in childhood are increasing. The current gold standard for treating pediatric obesity is eating habits and lifestyle modifications. The goal of our study was to determine the impact of a dietary intervention by means of the Mediterranean Diet and the Health Eating Plate on anthropometric and metabolic parameters in obese and overweight children.
Materials and methods: We studied a multi-ethnic population of 126 overweight/obese boys, including anthropometric measurements, blood biochemistry and nutrient intakes evaluation by means of Food Frequency Questionnaire at baseline, 6 and 12 months after a nutritional-behavioural intervention. Analysis of variance for repeated measures followed by Fisher’s Protected Least Significant Difference and Chi-squared test for trend was used to compare quantitative and qualitative variables. T-test for unpaired data was used for subgroups comparison. Associations were tested by regression analysis. Analyses were carried out by StatView Software (SAS Institute, Cary NC).
Results: Significant reductions in energy intake (expressed as kcal/kg body weight, from 37.9 ± 1.04 at baseline to 27.8 ± 0.85 after one year, p<0.001), protein intake (expressed as g/kg body weight, from 1.45 ± 0.04 at baseline to 1.16 ± 0.03 after one year, p<0.001), carbohydrates intake (expressed as g/kg body weight, from 5.47 ± 0.17 at baseline to 3.85 ± 0.12 after one year, p<0.001) and total fats intake (expressed as g/kg body weight, from 1.28 ± 0.04 at baseline to 3.85 ± 0.12 after one year, p<0.001) were observed. The proportion of obese boys decreased by 33% (chi square for trend 21.7, p<0.001). In obese boys, ALT decreased significantly after 1-year, in terms of absolute concentrations (F=9.150, p<0.001) and abnormal findings (chi test for trend: 7.50, p<0.05); these changes correlated with the reduction of BMI-SDS. Parameters of insulin resistance were associated with body and fat mass, with positive association with BMI-SDS detected for insulin, HOMA-IR, HOMA-B% (r=0.39, p<0.001; r=0.41, p<0.001; r=0.33, p<0.005, respectively) and negative association detected for 1/HOMA-IR, QUICKI and McAuley (r=0.44, p<0.001; r=0.46, p<0.001; r=-0.46, p<0.001, respectively). In obese boys, considering lipid profile, significant decreases were observed for total and LDL cholesterol.
Conclusion: 1-year nutritional-behavioral intervention in overweight and obese boys showed beneficial effects on metabolic and anthropometric risk factors
Beneficial effects on anthropometric and metabolic parameters in overweight and obese boys after 1 year nutritional-behavioral intervention
No full textBackground and aim: The prevalence of obesity and the risk for metabolic, cardiovascular, and liver diseases in childhood are increasing. The current gold standard for treating pediatric obesity is eating habits and lifestyle modifications. The goal of our study was to determine the impact of a dietary intervention by means of the Mediterranean Diet and the Health Eating Plate on anthropometric and metabolic parameters in obese and overweight children.
Methods: We studied a multi-ethnic population of 126 overweight/obese boys, including anthropometric measurements, blood biochemistry and nutrient intakes evaluation by means of Food Frequency Questionnaire at baseline, 6 and 12 months after a nutritional-behavioural intervention. Analysis of variance for repeated measures followed by Fisher’s Protected Least Significant Difference and Chi-squared test for trend was used to compare quantitative and qualitative variables. T-test for unpaired data was used for subgroups comparison. Associations were tested by regression analysis. Analyses were carried out by StatView Software (SAS Institute, Cary NC).
Results: Significant reductions in energy intake (expressed as kcal/kg body weight, from 37.9 ± 1.04 at baseline to 27.8 ± 0.85 after one year, p<0.001), protein intake (expressed as g/kg body weight, from 1.45 ± 0.04 at baseline to 1.16 ± 0.03 after one year, p<0.001), carbohydrates intake (expressed as g/kg body weight, from 5.47 ± 0.17 at baseline to 3.85 ± 0.12 after one year, p<0.001) and total fats intake (expressed as g/kg body weight, from 1.28 ± 0.04 at baseline to 3.85 ± 0.12 after one year, p<0.001) were observed. The proportion of obese boys decreased by 33% (chi square for trend 21.7, p<0.001). In obese boys, ALT decreased significantly after 1-year, in terms of absolute concentrations (F=9.150, p<0.001) and abnormal findings (chi test for trend: 7.50, p<0.05); these changes correlated with the reduction of BMI-SDS. Parameters of insulin resistance were associated with body and fat mass, with positive association with BMI-SDS
detected for insulin, HOMA-IR, HOMA-B% (r=0.39, p<0.001; r=0.41, p<0.001; r=0.33, p<0.005, respectively) and negative association detected for 1/HOMA-IR, QUICKI and McAuley (r=0.44, p<0.001; r=0.46, p<0.001; r=-0.46, p<0.001, respectively). In obese boys, considering lipid profile, significant decreases were observed for total and LDL cholesterol.
Conclusion: 1-year nutritional-behavioral intervention in overweight and obese boys showed beneficial effects on metabolic and anthropometric risk factors
T-cell epitopes of the major peach allergen, Pru p 3: Identification and differential T-cell response of peach-allergic and non-allergic subjects
No full textLipid transfer proteins (LTPs), particularly peach Pru p 3, are the most relevant plant food allergens in the South of Europe, and, therefore, their allergic properties have been extensively studied. However, neither T-cell epitopes nor their effect on the patients’ T-cell response has been investigated in any member of the LTP panallergen family. The objective of the present study was to map the major T-cell epitopes of Pru p 3, as well as to evaluate their induced T-cell response in peach-allergic versus control subjects. Thus, peripheral blood mononuclear cells (PBMCs) from 18 peach-allergic patients and Pru p 3-specific T-cell lines (TCLs) from 9 of them were cultured with Pru p 3 and with a panel of 17 derived peptides (10-mer overlapping in 5 amino acids representing the full sequence of Pru p 3). Proliferation in 5-day assays was carried out via tritiated-thymidine incorporation, while IL4 and IFNγ production was assessed via sandwich enzyme-linked immunosorbent tests (ELISA) of TCL culture supernatants. The results were compared to those obtained from 10 non-peach allergic control volunteers. Two consecutive peptides showed the highest activation capacity. About 74% of PBMCs and TCLs recognized them, forming a single T-epitope: Pru p 365–80. Additionally, other specific T-cell epitopes were observed. Pru p 325–35 was detected by more than 60% of TCLs from peach-allergic patients, and Pru p 345–55 only activated PBMCs from control subjects. Interestingly, TCLs from patients were associated with a Th2-type, whereas control TCLs presented a Th1-type cytokine response. The major immunogenic T-cell epitope identified in Pru p 3, Pru p 365–80, is a good candidate to develop new vaccines for hypersensitivity reactions associated with LTP allergens from Rosaceae fruits
Gad65 is recognized by t-cells, but not by antibodies from nod-mice
No full textSince the 64kDa-protein glutamic acid decarboxylase (GAD) is one of the major autoantigens in T-cell mediated Type 1 diabetes, its relevance as a T-cell antigen needs to be clarified. After isolation of splenic T-cells from non-obese diabetic (NOD) mice, a useful model for human Type 1 diabetes, we found that these T-cells proliferate spontaneously when incubated with human GAD65, but only marginally after incubation with GAD67, both recombinated in the baculovirus system. No effect was observed with non-diabetic NOD mice or with T-cells from H-2 identical NON-NOD-H-2g7 control mice. It has been published previously that NOD mice develop autoantibodies against a 64kDa protein detected with mouse beta cells. In immunoprecipitation experiments with sera from the same NOD mice and 33S-methionine-labelled GAD, no autoantibody binding could be detected. We conclude firstly that GAD65 is an important T-cell antigen which is relevant early in the development of Type 1 diabetes and secondly that there is an antigenic epitope in the human GAD65 molecule recognized by NOD T-cells, but not by NOD autoantibodies precipitating conformational epitopes. Our results therefore provide further evidence that GAD65 is a T-cell antigen in NOD mice, being possibly also involved in very early processes leading to the development of human Type 1 diabetes
Effects of cerebellar tDCS on glycometabolic control
No full textBackground and aims: The cerebellum is involved in motor, cognitive and glycometabolic control, as well as being a key structure in the pathophysiology of Parkinson's disease and psychiatric pathologies. It has been shown that cerebellar functions can be modulated by transcranial direct current stimulation (tDCS). The present research aims to study the effects of cerebellar tDCS on glycometabolic variable/glucose.
Methods: 14 healthy subject were recruited (6 Female; aged 25-55). We delivered cerebellar anodal, cathodal (2 mA, 20 minutes) and sham tDCS, in three separate sessions at intervals of at least 1 week. In each session, glucose was evaluated before (baseline T0), during (online: after 10 minutes T1, after 20 minutes T2) and 10 minutes after the end of the tDCS (T3), using a self-monitoring glucose sensor system.
Results: Anodal cerebellar tDCS significantly decreased glucose scores by about 2.57% at T1 [(mean±SD) T0 vs T1: 79.96±16 vs 77.90±13.47; p=0.04] while cathodal and sham cerebellar stimulation left it unchanged (p>0.05).
Conclusion: These results suggest that anodal cerebellar tDCS can reduce glucose in healthy subjects, thus arguing for a role of the cerebellum in glycometabolic process. Besides helping to understand the glucose processing, the possibility of modulating glucose by cerebellar tDCS might be relevant for developing novel therapeutic approaches to treat diabetic patients
Energy expenditure evaluation in humans and non-human primates by SenseWear Armband. Validation of energy expenditure evaluation by SenseWear Armband by direct comparison with indirect calorimetry.
No full textThe purpose of this study was to compare and validate the use of SenseWear Armband (SWA) placed on the arm (SWA ARM) and on the back (SWA BACK) in healthy humans during resting and a cycle-ergometer exercise and to evaluate the SWA to estimate Resting Energy Expenditure (REE) and Total Energy Expenditure (TEE) in healthy baboons.We studied 26 (15F/11M) human subjects wearing SWA in two different anatomical sites (arm and back) during resting and a cycle-ergometer test and directly compared these results with indirect calorimetry evaluation (IC), performed at the same time. We then inserted the SWA in a metabolic jacket for baboons and evaluated the TEE and REE in free living condition for 6 days in 21 (8F/13M) non-human primates.In humans we found a good correlation between SWA place on the ARM and on the BACK with IC during the resting experiment (1.1±0.3 SWAs, 1±0.2 IC kcal/min) and a slight underestimation in the SWAs data compared with IC during the cycle-ergometer exercise (5±1.9 SWA ARM, 4.5±1.5 SWA BACK and 5.4±2.1 IC kcal/min). In the non-human primate (baboons) experiment SWA estimated a TEE of 0.54±0.009 kcal/min during free living and a REE of 0.82±0.06 kcal/min.SWA, an extremely simple and inexpensive apparatus, provides quite accurate measurements of energy expenditure in humans and in baboons. Energy expenditure data obtained with SWA are highly correlated with the data obtained with "gold standard", IC, in humans
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