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Biomedical subjects

F Mercuri

Publications and source records attributed to F Mercuri.

At least 19 recordsLinked to original sources

Strain effects at the hexatic-B-smectic-A transition in the 65OBC liquid crystal.

We have studied the hexatic-B-smectic-A (HexB-SmA) transition in n -hexyl- 4'-n -pentyloxybiphenyl-4-carboxylate (65OBC) by means of a high-resolution ac photopyroelectric (PPE) calorimetric technique. A procedure for the interpretation of the PPE data, which allows the detection of an internal heating source due to strain annealing and/or latent heat, has been applied. We have found that the strain present in the sample depends on the kinetics of formation of the smectic phase once the sample is cooled from the isotropic one. The strain field keeps memory of this kinetics and can be only partially annealed on decreasing the temperature or cycling it around the Hex-SmA transition. A reversible ordering-disordering process has been found at T(c) and has been explained in terms of the competition between the order parameter variation with temperature and the constraints imposed by the disorder. The results confirm that the transition has a weakly first-order character with a specific heat critical exponent that disagrees with the available theoretical predictions. Our data show the importance of the disorder in 65OBC and we tried to clarify what would be the consequence of this result in theoretical modeling devoted to solving the puzzle of the HexB-SmA transition in this compound.

Journal Article↗

Dynamics of nematic liquid crystal with quenched disorder in the random dilution and random field regimes.

By means of specific heat spectroscopy, we have studied the dynamics of nematic 8CB nucleated, in the presence of random disorder, as the temperature is lowered across the isotropic to nematic phase transition such that the crossover region of random dilution to random field regimes of disorder strength is explored. We show, in terms of frequency dependence, hysteretic behavior, and aging effects, that the out-of-equilibrium properties of the nematic nucleated in the random disorder regime are strongly reminiscent of the bulk material while the one grown in the random field regime shows a glassy behavior with aging leading to slower dynamics. The aging effect has been explained in terms of strain relaxation in analogy with observations in other soft glassy colloidal systems.

Liquid Crystals↗

The microscopic switching mechanism of a [2]catenane.

We apply numerical simulations at an all-atom level to investigate the switching mechanism of a [2]catenane, a prototype of a molecular machine. This system is able to switch reversibly between two different stable states, upon external stimuli, with a time scale ranging from microseconds up to milliseconds, well over the typical domain of molecular dynamics (MD) computer simulations. However, combining a strategy recently developed for investigating rare events with ordinary MD, we are able to unravel the microscopic mechanism of the conformational rearrangements involved in the switching process, including dynamical effects. Along the path that connects the product and reactant state, we find several intermediate states characterized by pi-pi stacking interactions and hydrogen bonds. Moreover, counterions interact strongly with the system in a correlated way, in agreement with recent static calculations performed on [2]rotaxanes.

Journal Article↗

Critical behavior of thermal parameters at the smectic-A-hexatic-B and smectic-A-smectic-C phase transitions in liquid crystals.

High temperature resolution measurements of thermal conductivity, thermal diffusivity, and specific heat, with simultaneous polarized light visual inspection of the sample, have been performed at two different liquid crystal phase transitions: the SmA-SmC (Smectic-A-Smectic-C) and the SmA-HexB (Smectic-A-hexatic-B) in racemic A7 [4-(3-methyl-2-chlorobutanoyloxy)-4(')-heptyloxybiphenyl] and 65OBC (n-hexyl-4(')-n-pentyloxybiphenyl-4-carboxylate) compounds, respectively. In the past, anomalies in the thermal conductivity at the transitions have been reported. Our results indicate a nonsingular behavior of the thermal conductivity at both transitions, similarly to what has been previously reported for the smectic-A-nematic phase transition. It is also shown how, in several cases, the nature of the transition can be affected by the sample thermal history due to the presence of strain annealing phenomena.

Journal Article↗

Thermal and optical study of the kinetics of the nematic-isotropic transition in octylcyanobiphenyl.

It is shown in this paper that the kinetics of the nematic-isotropic (NI) transition in 30-microm-thick octylcyanobiphenyl liquid crystal films is strongly affected by the cell walls. We have found that this is due to the modification of the wetting properties of the liquid crystal depending on the surface treatment. The results have been obtained with an experimental setup which allows the simultaneous high resolution study of the sample thermal properties and texture evolution with temperature. An accurate determination of the width of the two phase coexistence region associated with the NI transition has been possible and it is shown that it is affected by the presence of a surfactant. The results have been interpreted with a simple model which is based on the possible presence of a well-defined interface between the nematic and the isotropic phases in the coexistence region, which depends not only on the thermal gradients in the sample but also on the surface treatments.

Journal Article↗

Small quartz silica spheres induced disorder in octylcyanobiphenyl (8CB) liquid crystals: a thermal study.

A photopyroelectric technique has been applied to the study of specific heat and thermal conductivity of homeotropically aligned mixtures of small quartz spheres (aerosil) and octylcyanobiphenyl (8CB) with concentration 0</=rho(s)</=0.04 g/cm(3). Thermal conductivity data show that, even at these very low concentrations, an annealing of the disorder introduced by the aerosil takes place on cooling at the smectic-A-nematic (Sm-A-N) phase transition and not only at the nematic-isotropic (N-I) one. This means that there is some elastic strain in the nematic phase of the sample which is not quenched. Accordingly the suppression of the N-I transition temperature as a function of rho(s) does not fit a random field with a random dilution model that accounts for random quenched disorder only. High resolution specific heat measurements at the A-N and N-I transition show the effect of the aerosil is not the same. While in the first case its peak is suppressed with increasing concentration, in the second case there are some indications that outside the two-phase coexistence region it is enhanced. The effect of surface-induced alignment is also discussed to explain some discrepancies between our data and the ones reported in literature. It is concluded that the amount of disorder in the sample does not depend on rho(s) only, but also on other variables such as external fields. Finally, a relaxation phenomenon in the aerosil network that partially compensate the disordering effect of the particles is suggested to explain the concentration dependence of the transition temperatures.

Journal Article↗

High-fructose diet decreases catalase mRNA levels in rat tissues.

Insulin resistance and hyperinsulinemia have recently been identified as independent determinants of several risk factors for cardiovascular disease. The generation of reactive oxygen species (ROS) may play an important role as a final common mediator by which glucose and insulin resistance might contribute to development of cardiovascular disease and hypertension. The aim of the present study was to evaluate changes on mRNA expression of antioxidant enzymes [catalase, Cu-Zn superoxide dismutase (Cu-ZnSOD), MnSOD], blood pressure and metabolic parameters in insulin resistance that follow feeding normotensive Wistar rats a high-fructose-enriched diet. In our investigation 26 normal male Wistar rats were fed a high-fructose diet for 2 weeks (no.=14) or normal chow to serve as a control group (no.=12). In vivo insulin resistance was verified in a subgroup of control and fructose-fed rats by the euglycemic hyperinsulinemic clamp technique at 2 different insulin infusion rates, 29 (submaximal stimulation) and 290 (maximal stimulation) pmol/kg/min respectively. The glucose infusion rate (GIR) was not significantly different in the two groups during the submaximal infusion of insulin (1.4 +/- 0.8 mmol/kg/min in fructose-fed rats vs 1.6 +/- 0.7 mmol/kg/min in control rats, NS) while in fructose-fed rats it was significantly lower (-29.8%) than in control rats during maximal infusion of insulin (2.6 +/- 0.3 mmol/kg/min vs 3.7 +/- 0.3 mmol/kg/min, p<0.05). Fructose feeding markedly reduced the expression of catalase mRNA and Cu-ZnSOD mRNA in the liver, catalase mRNA in the heart (p<0.05). A tendency of fructose feeding to reduce the expression of antioxidant enzymes in skeletal muscle and adipose tissue was also observed (NS). Fructose feeding also increased plasma uric acid (119.9 +/- 30.4 vs 42.1 +/- 10 pmol/l, p<0.05) and systemic blood pressure (128 +/- 4 vs 109 +/- 5 mmHg, p<0.05) respect to control animals. No significant changes were observed in plasma levels of glycemia and tryglycerides. Our study suggests that in non-hyperglycemic, fructose-fed insulin-resistant rats the expression of catalase is inhibited in liver and heart. This condition might lead to higher susceptibility to oxidative stress in insulin resistance. However, an adaptive cellular response to maintain the effectiveness of intracellular signaling pathways mediated by insulin-activated hydrogen peroxide generating systems may also be hypothesized.

Animals↗

Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress.

AIMS/HYPOTHESIS: Oxidative stress plays an important role in diabetic vascular complications. It has been shown that an imbalance in the ratio of nitric oxide: superoxide anion, because of a prevalence of superoxide anion, leads to an alteration in vascular reactivity. In this condition peroxynitrite production, resulting from the reaction between nitric oxide and superoxide, could increase. Peroxynitrite is responsible for nitration of tyrosine residues in proteins. Therefore, the presence of nitrotyrosine in plasma proteins is considered indirect evidence of peroxynitrite production. The aim of this study was to demonstrate the presence of nitrotyrosine in the plasma of patients with Type II (non-insulin-dependent) diabetes mellitus and to correlate its concentrations with the plasma concentrations of glucose and antioxidant defenses. METHODS: A total of 40 Type II diabetic patients and 35 healthy subjects were enrolled, and glycaemia, plasma nitrotyrosine, total antioxidant parameter and glycated haemoglobin were measured. Nitrotyrosine was detected by ELISA with a detection limit of 10 nmol/l. RESULTS: Nitrotyrosine was found in the plasma of all diabetic patients (means +/- SD = 0.251 +/- 0.141 micromol/l), whereas it was not detectable in the plasma of healthy control subjects. Nitrotyrosine plasma values were correlated with plasma glucose concentrations (r = 0.38, p < 0.02) but not with total antioxidant parameter or glycated haemoglobin. Total antioxidant parameter was reduced in diabetic patients (p < 0.01). CONCLUSIONS: The presence of nitrotyrosine in the plasma of diabetic patients indicates that peroxynitrite is generated in diabetes, suggesting a possible involvement of peroxynitrite in the development of diabetic complications.

Antioxidants↗

Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture.

To explore the effect of fluctuating glucose on endothelial cells, human umbilical vein endothelial cells were incubated for 14 days in media containing different glucose concentrations: 5 mmol/l, 20 mmol/l, or a daily alternating 5 or 20 mmol/l glucose. Apoptosis was studied by different methods: viability assay, cell cycle analysis, DNA fragmentation, and morphological analysis. Furthermore, the levels of Bcl-2 and Bax, well known proteins involved in apoptosis, were evaluated. Stable high glucose induced apoptosis in human umbilical vein endothelial cells, a phenomenon accompanied by a significant decrease of Bcl-2 and a simultaneous increase of Bax expression. However, apoptosis was enhanced in human umbilical vein endothelial cells exposed to intermittent, rather than constant, high glucose concentration. In this condition, Bcl-2 was not detectable, whereas Bax expression was significantly enhanced. These findings suggest that variability in glycemic control could be more deleterious to endothelial cells than a constant high concentration of glucose.

Apoptosis↗

Oxidative stress evaluation in diabetes.

Over the recent years, researches have focused their attention on the pathologic role of free radicals in a variety of diseases, among which the most important are atherosclerosis, cancer, and diabetes. The set of intracellular and extracellular conditions that leads to chemical or metabolic generation of reactive species is termed "oxidative stress." The susceptibility to oxidative stress is a function of the overall balance between the factors that exert oxidative stress and those that exhibit antioxidant capability. There is currently great interest in the potential contribution of increased oxidative stress to the development of complications in diabetes mellitus. Direct measurement of oxidative stress in vivo is a very complex question, because free radicals are highly reactive, have a very short life, and are present in very low concentrations. Thus, indirect methods, used for measuring secondary products of oxidative stress, are rather unspecific and may give conflicting data. Nitrotyrosine detection in plasma and tissues may be a useful method to demonstrate peroxynitrite-mediated damage. The total radical-trapping potential (TRAP) in plasma represents a more reliable estimation of serum antioxidant capability than the measurement of each known antioxidant. The detection of increased levels of oxidation products in tissue and biological fluids is important to investigate the relation between free radical production and the development of pathology. This hypothesis suggests the possibility of a therapeutic intervention with antioxidant agents. The identification of a useful marker to assess the effect of antioxidants on oxidative stress seems to be mandatory.

Antioxidants↗

Effects of fluctuations in the orientational order parameter in the cyanobiphenyl (nCB) homologous series

Photopyroelectric measurements of the anisotropy in the thermal conductivity Deltak vs temperature in the nCB (n=5,ellipsis,9) series are reported. The data have been used to deduce the behavior of the orientational order parameter Q close to the nematic-isotropic (N-I) and smectic A-nematic (A-N) phase transitions, respectively. It has been shown that near the N-I transition the data for 5CB and 6CB are consistent with the so-called "tricritical hypothesis," which predicts beta=0.25. This is not true for 7CB and 8CB in which the order parameter exhibits a behavior that could be caused by the presence of fluctuations that become increasingly important when the transition temperature is approached. A very simple model, which takes into account the contribution of fluctuations to the orientational order, has been developed close to the A-N transition and it has been shown that it is in good agreement with the experimental results. A semiquantitative explanation for the observed behavior in compounds with different nematic range has been also given.

Journal Article↗

Defective intracellular antioxidant enzyme production in type 1 diabetic patients with nephropathy.

There is an individual susceptibility to diabetic nephropathy, and oxidative stress is believed to play an important role in the pathogenesis of diabetic complications. Active oxygen species induce antioxidant enzyme expression in tissues, an effect considered to be a defensive mechanism. To test whether altered intracellular antioxidant enzyme production might explain the predisposition to diabetic nephropathy, we studied the effect of long-term (12 weeks) exposure to normal (5 mmol/l) or high (22 mmol/l) glucose concentrations on fibroblast antioxidant enzyme gene expression and protein activity in type 1 diabetic patients with and without nephropathy, nondiabetic nephropathic patients, and nondiabetic control subjects. Under conditions of normal glucose concentration in the culture media, CuZnSuperoxide-dismutase, MnSuperoxide-dismutase, catalase, and glutathione-peroxidase activity and mRNA expression were not different among the four groups. Under high-glucose conditions, CuZnSuperoxide-dismutase mRNA and activity increased similarly in all groups (P < 0.001 vs. basal), whereas MnSuperoxide-dismutase did not change. In contrast, catalase mRNA and activity as well as glutathione-peroxidase mRNA and activity increased in fibroblasts from type 1 diabetic patients without nephropathy (P < 0.001), in fibroblasts from nondiabetic nephropathic patients (P < 0.001), and in fibroblasts from nondiabetic control subjects (P < 0.001), but not in fibroblasts from type 1 diabetic patients with nephropathy. Exposure to high glucose concentrations significantly increased lipid peroxidation in cells, higher levels being found in cells from diabetic patients with nephropathy (P < 0.001). These data, while confirming that exposure to high glucose concentrations induces an antioxidant defense in skin fibroblasts from normal subjects, demonstrate a failure of this defensive mechanism in cells from type 1 diabetic patients with nephropathy, whereas skin fibroblasts from diabetic patients without complications or from nondiabetic nephropathic patients have an intact antioxidant response to glucose-induced oxidative stress.

Adult↗

Factor V leiden increases plasma F1+2 levels both in normal and deep venous thrombosis subjects.

BACKGROUND AND OBJECTIVE: A simple approach to understanding molecular mechanisms leading to thrombosis is the definition of how genetic factors influence biochemical parameters of coagulation. Conflicting data have been reported regarding the role that the genotype of factor V plays in the control of plasma F1+2 levels. The aim of this study was to test whether the factor V Leiden mutation affects F1+2 levels. DESIGN AND METHODS: We studied the effect of factor V Leiden mutation (detected by the polymerase chain reaction technique) on plasma F1+2 levels in 418 normal subjects and 39 subjects affected by deep venous thrombosis. RESULTS: In both normal subjects and those with venous thrombosis, heterozygotes for the Leiden mutation showed significantly higher plasma levels of F1+2 (p<0.0001 and p<0.005, respectively). Subjects with venous thrombosis had a higher allelic frequency of the Leiden mutation than normal subjects (11.5% and 3.1%, respectively). INTERPRETATION AND CONCLUSIONS: The results indicate that the genotype of factor V is a determinant of plasma F1+2 concentration. The allelic frequency of Leiden mutation in our normal subjects is higher than that found in other Italian populations but similar to that reported for populations of north- and middle-Europe. This finding is consistent with the peculiar ancestry and history of Friuli (the area in which subjects for this study were recruited), with respect to other Italian regions.

Adult↗

Disorder effects in low concentration dispersions of small quartz spheres in cyanobiphenyl liquid crystals.

A photopyroelectric study of the specific heat and the thermal conductivity of small quartz sphere (aerosil) dispersions in heptylcyanobiphenyl (7CB) and octylcyanobiphenyl (8CB) liquid crystals with a concentration rho(s)=0.005 g cm(-3) is reported. The thermal conductivity data show that, even at this low concentration, the elastic strain introduced in the liquid crystal by the aerosil particle is not completely annealed at the nematic-isotropic (NI) phase transition. In 8CB, annealing has been found at the smectic-nematic phase transition, while in the case of 7CB it occurs in the nematic phase also. Moreover, the depression of the NI transition temperature has been found to be much smaller than the one predicted by a random field model in which quenched disorder simply affects the average order of the sample and no effects of the elastic strain are considered.

Journal Article↗

Effect of intensive glycaemic control on fibrinogen plasma concentrations in patients with Type II diabetes mellitus. Relation with beta-fibrinogen genotype.

Recent studies show that in diabetic subjects an increase of plasma fibrinogen concentration is associated with a high risk of cardiovascular complications. Environmental and genetic factors contribute to the plasma fibrinogen concentration. Several studies indicate a relation between the polymorphism in the 5' region of the beta-fibrinogen gene and plasma protein concentrations and in diabetes the possible influence of hyperglycaemia on fibrinogen is still debated. In this study we investigated these relations. Hind III polymorphism was evaluated by a polymerase chain reaction-technique. On the basis of the observed allelic combination of fibrinogen beta-gene polymorphism and the existence of poor metabolic control (glycated haemoglobin > or = 7.5%), 50 Type II diabetic patients were selected. They were divided into three groups according to their beta-gene polymorphism (alpha1alpha1: n = 20, alpha1alpha2: n = 15, alpha2alpha2: n = 15) and then intensive insulin therapy was started. After 3 months of intensive treatment, the improvement in glycaemic control was equivalent, in terms of glycated haemoglobin, in all the three groups. A fibrinogen reduction was observed in alpha1alpha2 and alpha2alpha2 but not in alpha1alpha1 subjects. These results underline a possible relation between fibrinogen genotypes and glycaemic control in determining plasma fibrinogen concentrations in diabetic patients.

Blood Glucose↗

Pax-8 protein levels regulate thyroglobulin gene expression.

Pax proteins are transcription factors that control differentiation of several cell types. In adult organisms Pax-8 is expressed in the follicular thyroid cell where it interacts with sequences of thyroglobulin and thyroperoxidase promoters. In this study, we provide evidence indicating that Pax-8 protein levels regulate thyroglobulin gene transcription. The most critical approach consisted in increasing Pax-8 protein levels by transfecting thyroid cells with a Pax-8 expression vector. In this situation the thyroglobulin promoter transcriptional activity was significantly increased with respect to untransfected cells. In contrast, the transfection of thyroid transcription factor-1 (TTF-1) expression vector causes a modest decrease of thyroglobulin promoter activity, rather than an increase. Northern blots of human papillary cancers reveal a significant correlation between Pax-8 and thyroglobulin mRNAs. Gel-retardation assays suggest that the mechanism by which the Pax-8 protein levels modulate thyroglobulin promoter activity may occur through competition with TTF-1 for a common binding site. Since we also demonstrate that Pax-8 expression is subjected to TSH control, our data strongly suggest that Pax-8 protein levels could represent an important determinant for the regulation of thyroid cells.

Base Sequence↗

Recovery of Bilophila wadsworthiafrom Clinical Specimens in Italy.

This report is the first survey in Italy to evaluate the incidence of recovery of Bilophila wadsworthia in clinical situations. The survey was carried out at the departments of Microbiology in two Northern Italian hospitals over a one-year period. Tests for B. wadsworthia were carried out on a range of specimens from different body sites, when etiology by anaerobes was suspected. Out of a total of 350 samples examined, 67% were positive in bacteriological tests. Mixed anaerobic infections were detected in 53 specimens, corresponding to 23% of all cases. Strains of B. wadsworthia were isolated from 12 samples, equivalent to 5% and 22% of total and mixed/anaerobic infections, respectively. Bilophila wadsworthia was always isolated in mixed infections, mainly from the large intestine (67% of cases). The infectious process of B. wadsworthia was often complicated by abscess formation, regardless of body site. Interestingly, a strain was isolated from one case of bacteremia. The microorganisms most frequently isolated with B. wadsworthia were Escherichia coli for facultative species (38%), and Bacteroides fragilis, from anaerobic isolates (25%). Production of beta-lactamases by B. wadsworthia isolates was found in ten strains (83%), which appeared to be penicillin G resistant at concentration equal to or greater than the break-point (4 microg/mL). Epidemiological and clinical data from this and previous studies point to the involvement of B. wadsworthia in mixed infections. To assess the specific contribution of the species to the disease, studies of pathogenetic factors are to be considered in parallel. Nonetheless, production of beta-lactamases by most B. wadsworthia isolates could easily interfere with the therapeutical approach to infections involving the new species. The addition of a selective medium to culture specimens from the abdominal cavity should be considered in order to detect the presence of B. wadsworthia.

Journal Article↗

Glyceraldehyde 3-phosphate-induced DNA or protein modifications severely inhibit the protein/DNA interaction.

In this study, the effect of the reducing sugar glyceraldehyde 3-phosphate on protein/DNA interaction has been investigated. Treatment with glyceraldehyde 3-phosphate of oligonucleotides recognized by various transcription factors severely inhibits protein binding. The inhibitory effect is time and dose-dependent. Treatment with glyceraldehyde 3-phosphate of the homeodomain protein TTF-1 HD has also an inhibitory effect on the interaction with DNA, again in a time and dose-dependent manner. These "in vitro" effects could have "in vivo" counterparts and therefore contribute to molecular alterations observed either when intracellular protein are exposed to high doses of reducing sugars (i.e. in diabetes) or after a long time exposure (i.e. in Gzero-arrested cells during aging).

Animals↗