169,874 research outputs found

    Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles

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    Sebastiano Di Bucchianico,1 Maria Rita Fabbrizi,1 Silvia Cirillo,1 Chiara Uboldi,1 Douglas Gilliland,2 Eugenia Valsami-Jones,3,4 Lucia Migliore11Department of Translational Research and New Technologies in Medicine and Surgery, Medical Genetics Unit, University of Pisa, Pisa, Italy; 2European Commission-Joint Research Centre, Institute for Health and Consumer Protection, NanoBioSciences Unit, Ispra, Italy; 3School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, UK; 4Earth Sciences, Natural History Museum, Cromwell Road, London, UKAbstract: Gold nanoparticles (Au NPs) are used in many fields, including biomedical applications; however, no conclusive information on their potential cytotoxicity and genotoxicity mechanisms is available. For this reason, experiments in human primary lymphocytes and murine macrophages (Raw264.7) were performed exposing cells to spherical citrate-capped Au NPs with two different nominal diameters (5 nm and 15 nm). The proliferative activity, mitotic, apoptotic, and necrotic markers, as well as chromosomal damage were assessed by the cytokinesis-block micronucleus cytome assay. Fluorescence in situ hybridization with human and murine pancentromeric probes was applied to distinguish between clastogenic and aneuploidogenic effects. Our results indicate that 5 nm and 15 nm Au NPs are able to inhibit cell proliferation by apoptosis and to induce chromosomal damage, in particular chromosome mis-segregation. DNA strand breaks were detected by comet assay, and the modified protocol using endonuclease-III and formamidopyrimidine-DNA glycosylase restriction enzymes showed that pyrimidines and purines were oxidatively damaged by Au NPs. Moreover, we show a size-independent correlation between the cytotoxicity of Au NPs and their tested mass concentration or absolute number, and genotoxic effects which were more severe for Au NP 15 nm compared to Au NP 5 nm. Results indicate that apoptosis, aneuploidy, and DNA oxidation play a pivotal role in the cytotoxicity and genotoxicity exerted by Au NPs in our cell models.Keywords: Au nanoparticles, cytotoxicity, aneuploidy, oxidative DNA damage, micronuclei, particle siz

    The 15-lipoxygenase-modified high density lipoproteins 3 fail to inhibit the TNF-alpha-induced inflammatory response in human endothelial cells

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    Endothelial dysfunction represents one of the earliest events in vascular atherogenesis. Proinflammatory stimuli activate endothelial cells, resulting in an increased expression of adhesion molecules and chemoattractants that mediate leukocyte and monocyte adhesion, migration, and homing. High density lipoproteins (HDL) inhibit endothelial cell expression of adhesion molecules in response to proinflammatory stimuli. In the present work, we demonstrate that the modification of HDL(3) (the major and the most antiatherogenic HDL subfraction) by 15-lipoxygenase (15-LO), an enzyme overexpressed in the atherosclerotic lesions, impairs the anti-inflammatory activity of this lipoprotein. The 15-LO-modified HDL(3) failed to inhibit TNF-alpha-mediated mRNA and protein induction of adhesion molecules and MCP-1 in several models of human endothelial cells, and promoted inflammatory response by up-regulating the expression of such mediators of inflammation and by increasing monocyte adhesion to endothelial cells. Moreover, 15-LO-modified HDL(3) were unable to contrast the formation of reactive oxygen species in cells incubated with TNF-alpha, and increased the reactive oxygen species content in unstimulated cells. Activation of NF-kappaB and AP-1 was mainly involved in the expression of adhesion molecules and MCP-1 induced by 15-LO-HDL(3). Altogether, these results demonstrate that enzymatic modification induced by 15-LO impaired the protective role of HDL(3), generating a dysfunctional lipoprotein endowed with proinflammatory characteristics

    High density lipoprotein cholesterol levels are an independent predictor of the progression of chronic kidney disease

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    Objectives: Patients with chronic kidney disease (CKD) often present with reduced plasma HDL cholesterol (HDL-C) levels. Whether this reduction in an epiphenomenon or is involved in disease progression is unclear. The aim of this study was to investigate the relation between HDL-C levels/function and CKD progression in patients with different degrees of disease. Design: A total of 176 patients with CKD [glomerular filtration rate (GFR) 50.3 ± 29.1 mL min-1] were recruited and followed for up to 84 months. Lipid profile, metabolic status and kidney function were evaluated at predetermined times. Age-matched control subjects were selected from the PLIC study (n = 453). Scavenger receptor class B member 1 (SR-BI) and ATP-binding cassette transporter A1 (ABCA-1)-dependent efflux of cholesterol were measured in CKD patients and in age-matched control subjects. Results: Low HDL-C levels, diabetes and hypertension were associated with reduced GFR. At follow-up, low HDL-C levels were associated with earlier entry in dialysis or doubling of the plasma creatinine level (P = 0.017); HDL-C levels were the only lipid parameter that affected the progression of CKD (hazard ratio 0.951, 95% confidence interval 0.917-0.986, P = 0.007), independently of the presence of diabetes. Only SR-BI-mediated serum cholesterol efflux was significantly reduced in the group of CKD patients with low HDL-C levels compared to the control group. Conclusions: CKD patients with low levels of plasma HDL-C have a poor prognosis. HDL functionality is also impaired in renal dysfunction. These data support the relevance of HDL in influencing CKD progression

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Master bag low-oxygen packaging system: Quality evolution of ground beef patties during storage, blooming and display presentation

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    Case-ready ground beef patties have been packed using a low-oxygen master bag packaging system with oxygen scavengers consisting in: storage for 10 days in low oxygen master bag (0.5 C), blooming for different times and display life in air for 2 days (5 C). The kinetics of blooming was studied as well as the effect of a PVC stretch film (with an O2TR – oxygen transmission rate – equal to 20,000cm3m2 24 h1 (23 C, 0% RH, 1 bar of pO2) with or without perforation on myoglobin oxygenation and color changes. During storage in master bags, the scavengers allowed the progressive conversion of surface oxymyoglobin into deoxymyoglobin through the reversible formation of metmyoglobin (transient discoloration). The microflora shifted from aerobic to anaerobic with a predominance of lactic acid bacteria. The concentration of Brochotrix thermosphacta remained constant over the entire storage period. The removal of the trays from the master bag and the subsequent storage in air allowed the blooming of the meat within 60 min. The high O2TR value of the stretched PVC guaranteed rapid oxygen exchange, whereas the presence of the perforation did not contribute to a further increase in the superficial oxygenation. The quality decay during the display life was comparable to that of samples never stored in master bags. In conclusion, the use of low oxygen master bags was able to prolong the storage time on ground beef patties ensuring the current shelf life achieved with traditional packaging system

    Mitomycin C in highly myopic eyes - Author reply

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    Ophthalmology. 2005 Feb;112(2):208-18; discussion 219. Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes. Gambato C, Ghirlando A, Moretto E, Busato F, Midena E. SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy. Abstract PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes. DESIGN: Prospective, double-masked, randomized clinical trial. PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia. METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months). MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH. RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively). CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK. Comment in Ophthalmology. 2006 Feb;113(2):357; author reply 357-8

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Ruolo di materiali e sistemi di condizionamento in anossia nel prolungamento della shelf-life di carne equina case-ready

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    Una richiesta sempre più frequente è quella di individuare e/o ottimizzare soluzioni per estendere la shelf life di prodotti freschi porzionati e serviti in unità consumatore, al fine di raggiungere nuovi mercati e rispondere a specifiche esigenze di sostenibilità, garantendo qualità e sicurezza. Il presente lavoro ha avuto come obiettivo quello di valutare l’efficacia di diversi sistemi di conservazione per carne fresca di cavallo a fette, confezionata in unità consumatore contenenti atmosfera modificata priva di ossigeno. La carne equina infatti possiede caratteristiche nutrizionali che la differenziano dalle altre carni, soprattutto per l’elevato contenuto in ferro ed in acidi grassi polinsaturi. Queste caratteristiche rendono la carne equina molto sensibile all’ossigeno e il suo confezionamento è un processo delicato e complesso che richiede tecniche ed interventi opportuni. Nel corso della sperimentazione sono state testate le seguenti soluzioni: a) vassoi in polistirene espanso saldati con film laminato, entrambi ad alta barriera ai gas, con e senza assorbitori di ossigeno (OS) internamente al vassoio; b) vassoi in acido polilattico espanso (XPLA) chiusi con film barrierato in PLA, posizionati all’interno di “master bag” barriera; c) soluzione “case ready” descritta al punto b posizionata all’interno di “master bag”, con e senza assorbitori di ossigeno nello spazio di testa del sacco. Per la valutazione delle “performances” del sistema di confezionamento e la conseguente qualità del prodotto, sono state condotte analisi della composizione gassosa dello spazio di testa (“master bag” e vassoi), analisi microbiologiche, colorimetriche e sensoriali, e acquisizione delle immagini tramite scanner.L’inserimento di più unità di vendita in sacchi barriera e la presenza di assorbitori di ossigeno all’interno dei “master bag” diventa l’elemento discriminante per il mantenimento dei parametri qualitativi di carne conservata in soluzioni a base di XPLA. I risultati ottenuti indicano infatti che gli assorbitori d’ossigeno svolgono un ruolo fondamentale nel compensare le proprietà di barriera dei materiali a base di acido polilattico quando abbinati ad un confezionamento anossico in “master bag”. In queste condizioni, la carne equina raggiunge 15 giorni di conservazione a 0.5 ± 0.5°C, aprendo ad uno scenario distributivo che contempli l’impiego di bio-plastiche. Nelle soluzioni in cui i materiali ad alta barriera vengono usati in combinazione ai “master bag”, la doppia protezione del prodotto riduce fino ad annullare la forza motrice che regola gli scambi gassosi tra l’esterno e l’interno del vassoio, proteggendo la carne dall’esposizione all’ossigeno e consentendo il prolungamento della conservazione fino ad almeno un mese a 0.5 ± 0.5°C. In conclusione, la necessità di mantenere l’anossia per tutta la durata della conservazione, dalla distribuzione alla vendita, impone la selezione di materiali tradizionali ad alta barriera o di materiali di nuova concezione e con minore impatto ambientale come il PLA espanso, soprattutto se soluzioni attive vengono impiegate nel controllo degli scambi gassosi
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