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Biomedical subjects

G De Luca

Publications and source records attributed to G De Luca.

At least 19 recordsLinked to original sources

RAGE-NF-kappaB pathway activation in response to oxidative stress in facioscapulohumeral muscular dystrophy.

OBJECTIVES: An increased expression of adenine nucleotide translocator (ANT1), found in facioscapulohumeral muscular dystrophy (FSHD), is known to lead to a decrease in nuclear factor-kappaB (NF-kappaB) DNA binding and to sensitize muscle cells to oxidative stress and apoptosis. Receptor for advanced glycation end products (RAGE) mediated by NF-kappaB activation is involved in proinflammatory pathomechanism and in muscle fiber regeneration in inflammatory myopathies and in limb girdle muscular dystrophy. Oxidative stress can stimulate RAGE- NF-kappaB pathway. Our purpose was to verify if oxidative stress may induce RAGE- NF-kappaB pathway activation in FSHD, contributing to the pathogenesis of such a disease. MATERIALS AND METHODS: On muscle samples of eight patients with FSHD, eight patients with Duchenne muscular dystrophy and eight normal controls the following studies were carried out: immunocytochemistry for activated NF-kappaB; electrophoretic mobility shift assay of NF-kappaB DNA binding activity; Western blot studies of RAGE and ANT1; hydrogen peroxide (HP), peroxidase and glutathione peroxidase (GPx) assays. RESULTS: An increased RAGE and ANT1 expression in FSHD with moderate increase of NF-kappaB DNA binding activity was found together with an increased production of HP and a reduced activity of peroxidase and GPx. CONCLUSIONS: Our data confirm that response to oxidative stress and ANT1 increased activity are early events in FSHD muscle. The study also reveals that the RAGE- NF-kappaB pathway, induced by oxidative stress, is activated independently of the presence of a clear histochemical evidence of muscle damage in FSHD.

Adenine Nucleotide Translocator 1↗

Glutamate, water and ion transport through a charged nanosize pore.

The transport of transmitter, ions and water through a positively-charged nanopore was investigated through computer simulations. The physics of the problem is described by a coupled set of Poisson-Nernst-Planck and Navier-Stokes equations in a computational domain consisting a cylindrical pore, whose radius ranged from 1 to 8 nm and which was flanked by two compartments representing the vesicular interior and extra-cellular space. The concentration of co-ions is suppressed and of counter-ions enhanced, especially near the pore wall owing to electrostatic interactions. Glutamate (i.e. the transmitter considered) is negatively charged and is simulated as a counter-ion. The electro-kinetically induced pressure due to the movement of ions is negative and very pronounced near the pore wall where the concentration and flux of counter-ions is very high. The water velocity peaks in the pore center, diminishes to zero at the pore wall, but is constant along the pore axis. The mean velocity of the water/fluid is proportional to the vesicular pressure and pore cross-sectional area. Interestingly it is inversely related to the vesicular glutamate concentration. The factors determining the glutamate flux are complex. The diffusive flux generally predominates for narrow pore, and convective flux may dominate for wide pore if the vesicular pressure is high. Surprisingly at low vesicular pressure the mean total glutamate flux per unit cross-sectional pore area is higher for narrow pores. Higher flux is probably due to the rise of glutamate concentration in the nanopore, which is much more pronounced for narrow nanopores, due to the maintenance of approximate neutrality of charges in the pore and on the pore wall. In conclusion intra-vesicular pressure helps 'flushing-out' the transmitter, but the induced pressure 'drags-out' the water into the extra-cellular space.

Biological Transport↗

Molecular ordering and structure of quasi-spherical solutes by liquid crystal NMR and Monte Carlo simulations: the case of norbornadiene.

Norbornadiene (a C2v symmetry bicyclic rigid hydrocarbon) dissolved in three different nematic mesophases has been studied by liquid crystal NMR, to contribute to a better understanding of the influence of solvents on the solute's ordering and structure. The main results achieved by this work can be summarized as follows: (i) the order parameters obtained by the analysis of the 1H NMR spectra (at different temperatures) were successfully reproduced by a recently proposed model of solute/liquid crystal interactions, by using Monte Carlo numerical simulations; (ii) the theoretical (B3LYP/6-31++G**) "equilibrium" geometry of norbornadiene, vibrationally corrected by using the force field calculated at the same level, is compatible (within, at most, a 5% error) with experimental LXNMR data. This leads to the conclusion that the structure is not significantly distorted by the tested solvents.

Journal Article↗

Effects of different dietary protein intakes on body composition and vascular reactivity.

OBJECTIVE: To assess the effects of a diet rich in protein of animal origin in comparison to one with a protein intake of about 15% of the total daily calories on body composition and arterial function. DESIGN: Randomized prospective study with parallel groups. Body weight (BW), blood pressure (BP), main parameters of carbohydrate and lipid metabolism, body mass composition by bioelectrical impedance analysis, forearm blood flow at rest and in the postischaemic phase by strain gauge plethysmography and flow-mediated dilation of the brachial artery by echography were measured at baseline and after 6 months of the dietary intervention. SUBJECTS: In total, 15 clinically healthy male volunteers, regularly performing a mixed training three times weekly for 90 min. INTERVENTION: The participants were randomly prescribed a diet with high (1.9 g/kg BW) or normal (1.3 g/kg BW) protein content. STATISTICAL ANALYSIS: Differences between means were evaluated by the t-tests for paired or unpaired data and by one way analysis of variance. The strength of correlation between variables was investigated by bivariate Pearson correlation. RESULTS: Serum cholesterol significantly decreased with both diets in comparison to baseline values, whereas BW was slightly but significantly reduced only by the high-protein (HP) diet. No change was detected in BP and the other metabolic parameters. Body mass composition was not significantly modified by either diet. On the other hand, postischaemic flow-mediated dilation of the brachial artery was enhanced by the sole normal protein (NP) diet, whereas no change in the forearm blood flow, both at rest and in the postischaemic phase, was detected. CONCLUSIONS: These preliminary results indicate that HP diet was found to be not useful in increasing the muscle mass in comparison to a NP intake. In contrast to this, the latter diet seems to enhance the endothelial function of the arterial vessels with a more pronounced dilatation of the lumen in response to the increase in blood flow.

Adolescent↗

Obtaining the structure and bond rotational potential of a substituted ethane by NMR spectroscopy of solutions in nematic liquid-crystalline solvents.

Partially averaged dipolar couplings (also referred to as residual dipolar couplings) D(ij) can be obtained from the analysis of the NMR spectra of molecules dissolved in liquid-crystalline solvents. Their values for a nonrigid molecule depend upon the bond lengths and angles, the rotational potentials, and the orientational order of the molecules. The molecule studied, 1-chloro-2-bromoethane, is one of the simplest example of a substituted alkane in which the rotational potential has three minimum-energy positions, trans and gauche+/-conformations, and the present investigation explores the problems inherent in deriving the form of the potential and the molecular geometry from the set of partially averaged couplings between the protons, and between protons and (13)C nuclei. The geometrical parameters and the rotational potential obtained are compared with the results from a density-functional theory method.

Journal Article↗

Force balance conditions for droplet formation in cross-flow membrane emulsifications.

The membrane emulsification process is becoming of growing interest in many industrial fields. For monitoring the influence of process and membrane parameters on the droplet formation, quantitative information on the droplet detachment, during this process, is important. Until now, droplet formation has theoretically been described using computational fluid dynamics and global force equations. Unlike computational fluid dynamics methods, the global force models are less accurate but easier to handle and instructive. On this basis, in the present paper we present new force balance equations to describe droplet detachment during cross-flow membrane emulsification. In a first approximation, the droplet is supposed to grow leaning on the pore border as long as a force balance exists along the contact line located on the membrane surface. During this phase the base of the droplet, still stuck on the pore border, begins to bend on the membrane surface until its final detachment. Using force balance equations made along the contact lines, we obtain the minimum and maximum sizes that a droplet could have during cross-flow membrane emulsification. This approach is tested with different continuous phase velocities, membrane pore sizes and interfacial tensions. The results are compared to various experimental data, reported in literature. In particular, based on the experimentally found linear correlation between droplet and pore sizes, we show how the proposed balance equations can be used to obtain a satisfactory evaluation of the slopes of this linear correlation and how these force balances could be used to obtain an estimation of the interfacial tensions during the droplet formation.

Journal Article↗

Coronary stenting and abciximab in primary angioplasty for ST-segment-elevation myocardial infarction.

Advances in anti-platelet therapy and improvement of stent deployment techniques have improved the safety and efficacy of stenting in the setting of ST-segment-elevation myocardial infarction (STEMI). However, in randomized trials, routine coronary stenting does not reduce mortality and re-infarction, compared to balloon angioplasty. Further, the benefits in target vessel revascularization seem to be reduced when applied to unselected patients with STEMI. Direct stenting represents an attractive strategy with potential benefits in terms of myocardial perfusion. Future large randomized trials are needed to evaluate whether this strategy has a significant impact on outcome, and to provide a cost-benefit analysis of the unrestricted use of drug-eluting stents in this high-risk subset of patients. The additional use of abciximab reduces mortality in primary angioplasty. Since the feasibility of long-distance transportation has been shown in several randomized trials, early pharmacological pre-treatment may confer further advantages by early recanalization and shorter ischaemic time, particularly in high-risk patients. Further randomized trials are needed to clarify the potential benefits from early abciximab administration and the potential role of small molecules in primary angioplasty for STEMI.

Abciximab↗

C-reactive protein production in term human placental tissue.

OBJECTIVE: C-reactive protein (CRP) is a marker of systemic inflammation. Recently, it has been shown that CRP is present in amniotic fluid and fetal urine, and that elevated levels are associated with adverse pregnancy outcome. However, the precise source of amniotic fluid CRP, its regulation, and function during pregnancy is still a matter of debate. The present in vivo and in vitro studies were designed to investigate the production of CRP in human placental tissues. MATERIAL AND METHODS: Ten paired blood samples from peripheral maternal vein (MV), umbilical cord artery (UA) and umbilical vein (UV) were collected from women with elective caesarean sections at term. The placental protein accumulation capacity of hCG, hPL, leptin and CRP was compared with the dual in vitro perfusion method of an isolated cotyledon of human term placentae and quantified by ELISA. Values for accumulation (release) were calculated as total accumulation of maternal and fetal circuits normalized for tissue weight and duration of perfusion. For gene expression, RNA was extracted from placental tissue and reverse transcribed. RT-PCR and real-time PCR were performed using specific primers. RESULTS: The median (range) CRP level was significantly different between UA and UV [50.1 ng/ml (12.1-684.6) vs. 61 ng/ml (16.9-708.1)]. The median (range) difference between UV and UA was 9.3 ng/ml (2.2-31.6). A significant correlation was found between MV CRP and both UA and UV CRP levels. Median (range) MV CRP levels [2649 ng/ml (260.1-8299)] were 61.2 (6.5-96.8) fold higher than in the fetus. In vitro, the total accumulation rates (mean+/-SD) were 31+/-13 (mU/g/min, hCG), 1.16+/-0.19 (microg/g/min, hPL), 4.71+/-1.91 (ng/g/min, CRP), and 259+/-118 (pg/g/min, leptin). mRNA for hCG, hPL and leptin was detectable using conventional RT-PCR, while CRP mRNA could only be demonstrated by applying real-time RT-PCR. In the perfused tissue the transcript levels for the four proteins were comparable to those detected in the native control tissue. CONCLUSIONS: Our results demonstrate that the human placenta produces and releases CRP mainly into the maternal circulation similarly to other analyzed placental proteins under in vitro conditions. Further studies are needed to explore the exact role of placental CRP during pregnancy.

Adult↗

Effects of organic solvents on ultrafiltration polyamide membranes for the preparation of oil-in-water emulsions.

Hydrophilic ultrafiltration membranes made of polyamide with molecular weight cutoff 10 and 50 kDa have been studied for the preparation of oil-in-water emulsions by a cross-flow membrane emulsification technique. Isooctane and phosphate buffer were used as disperse and continuous phase, respectively. The permeation of apolar isooctane through the polar hydrophilic membrane was achieved by pretreatment of membranes with a gradient of miscible solvents of decreasing polarity to remove water from the pores and replace it with isooctane. Four different procedures were investigated, based on the solvent mixture percentage and contact time with membranes. After pretreatment, the performance of the membranes in terms of pure isooctane permeate flux and emulsion preparation was evaluated. The influence of organic solvents on polyamide (PA) membranes has been studied by SEM analysis, which showed a clear change in the structure and morphology of the thin selective layers. The effects proved stronger for PA 10 kDa than for 50 kDa. In fact, similar pretreatment procedures caused larger pore size and pore size distribution for PA 10 kDa than for 50 kDa. The properties of emulsions in terms of droplet size distribution reflected the membrane pore sizes obtained after pretreatment. The correlation between pore size and droplet size, for the physicochemical and fluid dynamic conditions used, has been evaluated.

Journal Article↗

Italian Right Hemisphere Language Battery: the normative study.

Clinical neurolinguistics still lacks consolidated and standardised tools for the assessment of impairments of pragmatics of verbal communication. In the present paper we present norms of the Italian version of the Right Hemisphere Language Battery (Batteria del Linguaggio dell'Emisfero Destro, BaLED) originally devised by Bryan. The normative study has been conducted with the recruitment of 440 healthy subjects. The battery of tests was not intended to be cognitively oriented, by providing evidence of the cognitive impairments underpinning verbal pragmatic deficits; on the contrary, it permits the detection of the presence/absence of impairments in processing the main pragmatic features of verbal communication traditionally associated with right hemisphere lesions. Thus, apart from being a clinical tool for diagnosing pragmatic impairments of verbal communication, the BaLED represents a useful initial battery of tests for clinical assessment and for selecting specific populations of neurological patients suitable for investigation in further experimental studies.

Adult↗

Legionella waterline colonization: detection of Legionella species in domestic, hotel and hospital hot water systems.

AIMS: An evaluation was made of the prevalence of Legionella species in hot water distribution systems in the city of Bologna (Italy) and their possible association with bacterial contamination (total counts and Pseudomonadaceae) and the chemical characteristics of the water (pH, Ca, Mg, Fe, Mn, Cu, Zn and Total Organic Carbon, TOC). METHODS AND RESULTS: A total of 137 hot water samples were analysed: 59 from the same number of private apartments, 46 from 11 hotels and 32 from five hospitals, all using the same water supply. Legionella species were detected in 40.0% of the distribution systems, L. pneumophila in 33.3%. The highest colonization was found in the hot water systems of hospitals (93.7% of samples positive for L. pneumophila, geometric mean: 2.4 x 10(3) CFU l(-1)), followed by the hotels (60.9%, geometric mean: 127.3 CFU l(-1)) and the apartments with centralized heating (41.9%, geometric mean: 30.5 CFU l(-1)). The apartments with independent heating systems showed a lower level of colonization (3.6% for Legionella species), with no evidence of L. pneumophila. Correlation analysis suggests that copper exerts an inhibiting action, while the TOC tends to favour the development of L. pneumophila. No statistically significant association was seen with Pseudomonadaceae, which were found at lower water temperatures than legionellae and in individual distribution points rather than in the whole network. CONCLUSIONS: The water recirculation system used by centralized boilers enhances the spreading of legionellae throughout the whole network, both in terms of the number of colonized sites and in terms of CFU count. SIGNIFICANCE AND IMPACT OF THE STUDY: Differences in Legionella colonization between types of buildings are not due to a variation in water supply but to other factors. Besides the importance of water recirculation, the study demonstrates the inhibiting action of copper and the favourable action of TOC on the development of L. pneumophila.

Environmental Monitoring↗

Distribution of the mutated delta 32 allele of the CCR5 gene in a Sicilian population.

The CCR5 gene encodes a cell-surface chemokine receptor molecule that serves as a co-receptor for macrophage-tropic strains of human immunodeficiency virus type 1 (HIV-1). A mutation in this gene may alter the expression or the function of the protein product, thereby altering chemokine binding and/or signalling or HIV-1 infection of cells that normally express CCR5 protein. Individuals homozygous for a 32-bp deletion allele of CCR5 (CCR5 delta32), heritable as a Mendelian trait, are relatively resistant to HIV-1 infection. The CCR5 delta32 mutation is present in the Caucasian population at different frequencies. The aim of this study was to investigate the frequency of truncated alleles of the CCR5 delta32 gene in a Sicilian population, as the interpopulation variation in CCR5 delta32 frequency may be a significant factor in the prediction of AIDS endemicity in future studies. We examined 901 healthy individuals from several Sicilian provinces. We found a mean (+/- standard deviation) delta32 allele frequency (fr) of 0.04 +/- 0.012. The highest value was observed in the province of Messina, with a mean delta32 allele frequency of 0.06 +/- 0.024, where we collected samples from a cohort of 114 HIV-1-infected individuals. The observed frequency amongst these patients was quite low (fr = 0.03 +/- 0.031) compared to the healthy population, although the difference was not statistically significant.

Adolescent↗

Late reopening of an occluded infarct related artery improves left ventricular function and long term clinical outcome.

OBJECTIVE: To assess effects on left ventricular (LV) function and on long term clinical outcome of late percutaneous transluminal coronary angioplasty (PTCA) of a chronically occluded infarct related artery. METHODS: 65 patients who underwent PTCA a mean (SD) of 6.0 (1.2) months after a previous myocardial infarction were divided in two groups according to dilated artery patency status after PTCA: group 1 (35 patients with TIMI (thrombolysis in myocardial infarction) grade 3 flow) and group 2 (30 patients with TIMI grade 0-2 flow). Echocardiography was performed at admission and at six months' follow up. A three year follow up was conducted with major adverse cardiac events (MACE) as end points. RESULTS: At follow up, group 1 had improved global LV ejection fraction (48.7% v 43.6%, p < 0.001) and LV indexed end diastolic and end systolic volumes (75 v 86 ml/m(2) and 40 v 53 ml/m(2), respectively, p = 0.011) compared with group 2. Kaplan-Meier analysis showed a higher incidence of cardiac death (p = 0.02) and MACE (p < 0.0001) in group 2. TIMI 3 after PTCA was an independent predictor of event-free survival at follow up. CONCLUSION: Late PTCA of a chronically occluded infarct related artery improves LV function, reduces cardiac death, and improves long term clinical outcome.

Angioplasty, Balloon, Coronary↗

Is routine stenting for acute myocardial infarction superior to balloon angioplasty? A randomised comparison in a large cohort of unselected patients.

OBJECTIVE: To evaluate the impact of routine stenting, compared with balloon angioplasty, in unselected patients presenting with ST segment elevation myocardial infarction (STEMI). DESIGN: Randomised trial. SETTING: Tertiary referral centre. PARTICIPANTS: All patients presenting with STEMI randomly assigned to stenting or balloon angioplasty. No exclusion criteria were applied. MAIN OUTCOME MEASURE: The primary end point was combined death or reinfarction at one year's follow up. RESULTS: 1683 consecutive patients with STEMI were randomly assigned before angiography to stenting (n = 849) or balloon angioplasty (n = 834). A total of 785 patients (92.5%) in the stent group and 763 patients (91.5%) in the balloon group actually underwent primary angioplasty. The groups were comparable in terms of postprocedural TIMI (thrombolysis in myocardial infarction) flow, myocardial blush grade, and distal embolisation. No difference was observed in clinical outcome at both intention to treat (14% v 12.5%, not significant) and actual treatment analyses (12.4% v 11.3%, not significant). CONCLUSIONS: Compared with balloon angioplasty, routine stenting does not seem to reduce death and reinfarction in a large cohort of unselected patients with STEMI.

Angioplasty, Balloon↗

Decreased integrin gene expression in patients with MS responding to interferon-beta treatment.

Interferon-beta (IFN-beta) ameliorates disease course in a subset of patients with MS. The reasons for heterogeneity of clinical responses, however, are unclear. We assessed possible effects of IFN-beta on the gene expression of the leukocyte adhesion molecules VLA-4 and LFA-1 during the first year of treatment of 50 patients with relapsing-remitting MS who showed differential clinical responses. We observed a significant reduction of VLA-4 (P=0.002) and LFA-1 (P=0.03) mRNA expression compared to baseline in first-year clinical responders (n=22). In contrast, first-year IFN-beta non-responders (n=28) had unchanged levels of VLA-4 and LFA-1. In vitro treatment of PBMC with IFN-beta indicated a direct effect on transcription of the integrins' genes. Transcriptional downmodulation of adhesion molecules during IFN-beta treatment may contribute to its mode of action in MS.

Adjuvants, Immunologic↗

Clinical improvement and serum amino acid levels after mud-bath therapy.

Spa therapy is an ancient approach to degenerative diseases such as osteoarthritis, but until today this tradition has been predominantly empiric and intuitive and few studies have focused on the biological changes derived from this treatment. We assessed the clinical efficacy and variations in amino acid concentrations in serum samples from patients with knee osteoarthritis who underwent spa therapy and put forward an explanation of their role in clinical improvement. Thirty-one patients with knee osteoarthritis who underwent spa therapy underwent a clinical evaluation, and serum amino acid levels were assayed before and after a cycle of balneotherapy and mud-pack therapy. The thermal treatments were carried out in Sciacca. Analysis of the data showed a significant reduction in pain and improvement in joint motility. Serum concentrations of tryptophan, cysteine and citrulline were significantly higher than at baseline. No significant differences were observed in serum levels of the remaining free amino acids. The results of this study confirm the efficacy of spa therapy in the treatment of osteoarthritis. A possible role for changes in serum amino acid concentration is discussed.

Amino Acids↗