751 research outputs found

    ANTIMICROBIAL AND ANTIBIOFILM ACTIVITIES OF BIOGENIC SELENIUM NANOPARTICLES: A CONTRIBUTION TO THE DEVELOPMENT OF AN ALTERNATIVE STRATEGY AGAINST THE ANTIBIOTIC RESISTANCE CONCERN

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    Bacterial biofilms are microbial communities embedded in a highly hydrated exopolymer (EPS) matrix and can exist on different biotic and abiotic surfaces. The presence of these protective EPS matrix allows biofilms to survive in harsh environmental conditions and to resist to antiobiotic action, representing a challenge for the common antimicrobial therapy. Recently, a wide range of nanoparticles (i.e. silver, gold, iron oxide) have been intensively studied as antimicrobial agents including their use against multidrug-resistant (MDR) bacteria. In the present study the physiochemical characteristics of biogenically produced Selenium Nanoparticles were evaluated along with their antimicrobial and antibiofilm activity

    In vivo and in vitro data supporting the involvement of oxidative stress in aging-related and metabolic diseases

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    Background: Oxidative stress (OxS) is caused by the derangement of the balance between production of oxidants, mainly represented by reactive oxygen species (ROS), and the antioxidant’s ability to detoxify them. The consequent biomolecular oxidative damage tends to accumulate in aged biological systems and it is widely believed to act as main trigger of aging- and metabolism- related diseases such as late onset Alzheimer’s disease (LOAD), postmenopausal osteoporosis (PO) and metabolic syndrome (MetS). The involvement of OxS in these pathologies has been nicely demonstrated in vitro and animal models. In contrast, the data from human studies are scarce and highly controversial. Similar controversies feature the body of population-based studies on the effects of antioxidant supplements or dietary interventions on OxS and related diseases. Objectives: To address these issues we have conducted three research projects with the following aims: Project 1: to evaluate a possible cross-sectional and/or longitudinal association between systemic markers of oxidative stress and the most common dementia-related diseases (Alzheimer’s disease and vascular dementia). Projects 2: to evaluate a possible involvement of OxS in the development of PO. Project 3: to evaluate in vitro the effects of flavonoids, in particular (-)-epicatechin (EC) and its metabolites (ECM), on the regulation of expression and activity of NADPH oxidase in hepatic cells (HepG2) treated with palmitate (Pal). Material and methods: Project 1: The patients enrolled (n=476 subjects) were divided, in accordance to the diagnosis of dementia, in: 105 late onset Alzheimer disease (LOAD), 54 vascular dementia (VaD), 199 mild cognitive impairment (MCI), which is consider as an intermediate state between normal aging and dementia, and 118 healthy controls. Among the MCI patients, a subgroup of 111 patients were follow-up for an average of 2 years (2.0 ± 0.6 years). The serum markers of OxS assessed in each subjects were: hydroperoxides (HY), advance oxidation protein products (AOPP), total antioxidant power (TAP), residual antioxidant power (RAP), uric acid (UA), and thiols (TH) Project 2: 290 women (age spanning from 21 to 65 years) were enrolled and divided in different groups according to menopausal status (reproductive age, peri- and post-menopause). In these women, serum markers of OxS (HY, AOPP, 8-isoprostane-F2-iso, 8-hydroxy-2'-deoxyguanosine-8-OH-dg, TAP, RAP, UA and TH) and serum bone markers (Bone-specific Alkaline Phosphatase-BAP and C-terminal telopeptide of type I collage-CTX-1) were assessed. Furthermore the areal bone density at lumbar spine, hip and total body by was assessed by dual energy X-ray absorptiometry (DXA) scanner. Project 3: HepG2 cells were incubated for 24 h with Pal (0.25 mM), in the absence/presence of EC (0.25-1 μM) and ECM (1 μM). By Real-Time PCR (RT-PCR) and western blot, mRNA and protein expression levels of NADPH oxidase subunits (NOX3, p22phox, p47phox) were assessed. Moreover, protein expression levels of insulin resistance pathway (IKK and JNK) were assessed by western blot as well. NADPH oxidase activity and cell oxidants were measured respectively with chemiluminescence assay and oxidant-sensitive probe 5-(and-6)-carboxy-2,7 dichlorodihydrofluorescein diacetate (DCF). Lipid accumulation was assessed by Red Oil O staining. Results: Project 1: Analysis of covariance showed that an oxidative derangement (high HY and/ low antioxidants) were present in MCI, LOAD and, though less pronounced in VaD. Multivariate logistic regression analysis showed that, compared with controls, high levels (over median value) of serum hydroperoxides were independently associated with an increase in the likelihood of having MCI (Odd Ratio: 2.59, 95% Confidence Interval: 1.08-6.21) or LOAD (OR: 4.09, 95%CI: 1.36-11.81). Moreover, low levels of residual antioxidant power were associated with increased risk of having MCI (OR: 3.97, 95% CI: 1.62- 9.72), but not LOAD (OR: 2.31, 95%CI: 0.83-6.63). No differences in either of these two OxS markers were found by comparing MCI patients who converted (n = 29) or not converted (n = 82) to LOAD. Project 2: Pearson’s correlation showed that increased serum levels of a lipid peroxidation marker, HY, were negatively and independently associated with decreased bone mineral density (BMD) in total body (r=-0.192, p<0.05), lumbar spine (r=-0.282, p<0.01) and total hip (r=-0.282, p<0.05), as well as with increased bone resorption rate (r=0.233, p<0.05), as assessed by the serum concentration of CTX-1. Importantly, multiple regression analysis revealed that HY is a determinant and independent factor for the association between lumbar spine BMD and CTX-1 levels. Project 3: Data obtained in vitro showed that Pal increases the production of oxidants in HepG2 through an up-regulation of protein levels and mRNA expression of NOX3. Pal was able to “mimic” an insulin resistance condition through an up-regulation of JNK and IKK expression. Moreover, our results demonstrated that EC and ECM decrease the activity of NADPH oxidase and the ROS production; furthermore, both EC and ECM decreased the expression of JNK and IKK, improving the insulin resistance condition. The Oil Red O staining showed that EC and ECM cannot significantly prevent Pal-induced lipid accumulation. Conclusion: Systemic OxS might be a significant feature of LOAD, PO and MetS. Moreover, our results suggest that rich-flavonoids food consumption may be an important way of prevention of age- and metabolism-related diseases. Abbreviations: OxS, oxidative stress; MCI, mild cognitive impairment; LOAD, late onset Alzheimer’s disease; VaD, vascular dementia; HY, hydroperoxides; AOPP, advanced oxidation protein products; TAP, total antioxidant power; RAP, residual antioxidant power; UA, uric acid; TH, thiol; BMD, bone mineral density; OR, Odds Ratio; EC, (-)-epicatechin; ECM, (-)-epicatechin metabolites; Pal, palmitate

    (-)-Epicatechin prevents palmitate-induced increase in NADPH oxidase expression and activation in the human hepatocyte cell line HepG2

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    Background: The incidence of metabolic syndrome (MetS) in the world’s adult population is increasing and is becoming an important health problem given that it can lead to insulin-resistance and type 2 diabetes. MetS-associated insulin-resistance can be in part triggered by the associated increased plasma levels of free fat acid (FFAA). The activation by FFAA of NADPH oxidase and the consequent production of superoxide anion and derived oxidants can in part lead to hepatic insulin resistance. Oxidants can activate kinases (JNK, IKK) which negatively phosphorylate the insulin receptor and IRS1 leading to an impaired insulin signaling. Epidemiological studies show that the consumption of fruit and vegetables in humans decreases the risk for MetS. The flavan-3-ol (-)-epicatechin (EC) is present in large amounts in fruit and vegetables. Furthermore, we have shown that EC improves parameters of inflammation and insulin sensitivity in adipocytes. Objective: The aim of this study was to evaluate the effects of EC and its metabolites on the expression and activity of NADPH oxidase, and the consequent production of oxidants, in human hepatocytes (HepG2 cells) treated with the FFAA palmitate (Pal). Material and Methods: HepG2 cells were incubated with Pal (0.25-0.75 mM), in the absence and the presence of EC and EC metabolites (ECM) (0.25-1 μM) for 24 h. The protein levels of NADPH oxidase subunits (NOX3, p22, p47) were assessed by Western Blot. NADPH oxidase activity was measured by lucigenin-enhanced chemiluminescence assay and cell oxidants by fluorescence with the oxidant-sensitive 5-(and-6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate (DCF) probe. Results: Pal caused a dose-dependent increase in the HepG2 cell expression of NOX3 and p22. EC and its metabolites acted preventing Pal-induced NOX3 and p22 expression. The incubation with Pal also caused a significant increase in NADPH oxidase activity, measured by both enzyme activity, and p47 translocation from the cytosol to the membrane. EC and ECM (1 μM) prevented Pal-mediated NADPH oxidase activation. Pal also caused an increase in cellular oxidants (DCF fluorescence) which was significantly decreased by EC and ECM. Conclusion: Results show that PAL increases the production of oxidants in HepG2 through an up regulation of NOX3/p22 expression. EC and its metabolites, at concentrations found in plasma after consumption of EC-rich foods, prevented Pal-induced activation of NADPH oxidase and increased oxidant production. This EC effects could be relevant in the improvement of insulin sensitivit

    Value of ancient cartography for geoenvironmental purposes. A case study from the Po River delta coast (Italy).

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    A set of four large-scale pregeodetic maps was studied. They depict the Po River delta ancestor in the late-16th century AD (before the year 1604), an extremely important area for the geoenvironmental and historical evolution of Northern Italy at the beginning of the Little Ice Age. The maps are very detailed and complex. This characteristic involves some problems relating to accuracy and comparison with present-day cartography. This first attempt at map georeferencing is required in order to make possible original coastline location in areas that do not exist today because of sea erosion. Nevertheless, a further attempt is already being made for achieve a better understanding of the maps. Inner details and manifest errors were highlighted so as to better appraise the reliability of the maps and the authors’ survey methodologies. Furthermore, a particular and highly peculiar geomorphological object (i.e. an offshore megabank) was analyzed and rejected as a completely untrue ancient landscape tract. Hence, the really interdisciplinary character of this kind of studies must be ever taken into consideration and critical map analysis should not merely be seen as a useless and time-consuming analytical tool since the fortuitous preservation of ancient documents can dispel wayward interpretations in geoenvironmental reconstruction. The results of the study portray the many problems relating to the local coastal evolution, more interesting than had been believed up to now. The existence of four different maps representing the same geographical area in the same short (decadal) time span is a fortuitous and very rare historical case, as well as being a unique opportunity. The maps reproduce the same objects with an astonishingly high degree of accuracy even if there is no robust geographical frame capable of providing a definite points location. The most problematic factor is the impossibility of a reliable restitution of the original eroded coastline. Hence the need to apply a more appropriate and more accurate georeferencing method becomes quite evident. In spite of this drawback, the multiple comparison allows us to state that the Aleotti map (1D) cannot be assumed to be a reliable data source for inferences concerning the 16th century coastal and marine dynamics nor the fluvial sediment transport rates notwithstanding its undoubted scenographic value. Only mere chance was responsible for the broad diffusion and knowledge of this historical map across the European cultural environment of the 17th -18th centuries. If the megabank was not a real natural object, then it is possible that it could have originated from a bad copy job from the maps of other authors (Fabri?) or even from an attempt by Aleotti to suggest a personal interpretative model for the local coastal erosion occurring in the last decade of the 16th century, resulting from a merging of various sources of information, modified by an author’s experience acquired in the southern delta reaches. In any case, that information source appears to be rather dated. Hence, at times the casual nesting of a set of compelling evidence and suggestions offered up by the ancient primary data sources can be a very dangerous analytical tool unless it is supported by an adequate critique. Nevertheless, the question as to what the real truth of the information content offered by an ancient map corresponds remains unanswered: that is, if it is the one proposed by the original document or, conversely, the one suggested by the georeferenced derived-sample

    Festival della ricerca 2011 Università di Ferrara Primo premio

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    UNA BUONA DIFESA DAI RADICALI LIBERI PUO' ESSERE UN'ARMA EFFICACE CONTRO L'OSTEOPOROSI POST-MENOPAUSALE I radicali liberi essendo i responsabili dell’invecchiamento possono essere una delle cause dell’osteoporosi post-menopausale? Gli antiossidanti, molecole in grado di proteggere il nostro organismo dall’azione dei radicali liberi, possono avere un ruolo nella prevenzione e nel contrasto dell’osteoporosi post-menopausale? Sono state reclutate 103 donne in menopausa alle quali è stata eseguita una densitometria ossea (DEXA) per valutare lo stato di salute dell'osso. Inoltre da ogni donna è stato prelevato un campione di sangue sul quale sono stati misurati: radicali liberi antiossidanti,CTX-1 indicatore della velocità di degradaIl calo delle difese antiossidanti nelle donne osteopeniche ed osteoporotiche facilita l’attacco dei radicali liberi nei confronti dell’osso I radicali liberi risultano direttamente coinvolti nell’origine dell’osteoporosi post-menopausale, poiché influenzano la velocità di degradazione dell’osso

    Anthocyanin actions at the gastrointestinal tract: Relevance to their health benefits

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    Anthocyanins (AC) are flavonoids abundant in the human diet, which consumption has been associated to several health benefits, including the mitigation of cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver disease, and neurological disorders. It is widely recognized that the gastrointestinal (GI) tract is not only central for food digestion but actively participates in the regulation of whole body physiology. Given that AC, and their metabolites reach high concentrations in the intestinal lumen after food consumption, their biological actions at the GI tract can in part explain their proposed local and systemic health benefits. In terms of mechanisms of action, AC have been found to: i) inhibit GI luminal enzymes that participate in the absorption of lipids and carbohydrates; ii) preserve intestinal barrier integrity and prevent endotoxemia, inflammation and oxidative stress; iii) sustain goblet cell number, immunological functions, and mucus production; iv) promote a healthy microbiota; v) be metabolized by the microbiota to AC metabolites which will be absorbed and have systemic effects; and vi) modulate the metabolism of GI-generated hormones. This review will summarize and discuss the latest information on AC actions at the GI tract and their relationship to overall health benefits.Fil: Oteiza, Patricia I.. University of California at Davis; Estados UnidosFil: Cremonini, Eleonora. University of California at Davis; Estados UnidosFil: Fraga, César Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentin

    P3‐087: Late‐onset Alzheimer disease and vascular dementia are precociously associated with a derangement in systemic oxidative balance

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    Growing in vitro and animal evidence suggests a crucial role of oxidative stress (OxS) in the neurodegenerative process occurring in late Alzheimer’s disease (LOAD) and Vascular Dementia (VAD). However, thus far, in vivo studies conducted onliving humans failed to definitely proved the implication of oxidative mechanisms in the onset and progression of these two major forms of dementia. In the attempt to address this issue we evaluated a pattern of multiple peripheral markers of OxS in large sample including 223 mild cognitive impairment (MCI), 162 LOAD, 65 VAD and 143 older normal cognitive controls. Methods:The sample subjects were evaluated for serum markers of biomolecular oxidative damage (lipid hydroperoxides and advanced oxidation protein products) along with enzymatic (arylesterase and paraoxonase activities of PON-1 and Ferroxidase I and II activities) and non-enzymatic [residual antioxidant power (RAP)], protein thiols and uric acid) antioxidants. Results: Multivariate analysis (covariates: age, gender, smoking and comorbidities) of our data showed a significant increase (p<0.05) of hydroperoxides in LOAD patients (+30.6 %), (but not in MCI and VAD) with respect to controls. Moreover, residual antioxidant power emerged as significantly lower in MCI (-24.5%), LOAD (-24.2%) and VAD (-29%) patients, compared to controls (p<0.01 for all). The trend towards a worse oxidative balance in demented patients was further confirmed by the results obtained with the assessment of arylesterase activity, which was independently associated with the likelihood of having MCI [odds ratio (OR): 2.3; 95% confidence intervals (CI): 1.3-3.8], LOAD (O.R.: 2.8; 95% CI: 1.5 – 5.0) or VAD (O.R.: 2.7; 95% CI: 1.3 – 3.8). Conclusions: Overall, our data indicate that a dysregulation of systemic antioxidant defences may play a role in the onset of dementia-related diseases. Indeed, a significant derangement in redox balance imbalance appears to be already present in the prodromal stage of dementia. If confirmed by other studies, our results might indirectly support the use of dietary antioxidants in order to rebalance the altered redox homeostasis in patients affected by MCI and LOAD

    (–)-Epicatechin in the control of glucose homeostasis: Involvement of redox-regulated mechanisms

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    Emerging evidence supports a beneficial action of the flavan-3-ol (–)-epicatechin (EC) on insulin sensitivity and potential impact on the development/progression of type 2 diabetes (T2D). In humans, supplementation with EC-rich foods, extracts, and pure EC improves insulin sensitivity and glucose tolerance in normal weight, overweight, obese and T2D individuals. These effects of EC are also observed in rodent models of diet-induced obesity and T2D. The events involved in the development of insulin resistance and T2D are multiple and interrelated. EC has been shown to inhibit inflammation, oxidative and endoplasmic reticulum stress, to modulate mitochondrial biogenesis and function, and to regulate events in the gastrointestinal tract and the pancreas that impact glucose homeostasis. A downregulation of oxidant production, particularly through direct inhibition or suppression of NADPH oxidase expression, and of redox sensitive signals (NF-κB, JNK1/2) that inhibit the insulin pathway, appear to be central to the beneficial actions of EC on insulin sensitivity. Overall, EC seems to have a positive role in the regulation of glucose homeostasis, however definitive answers on its importance for the management of T2D will depend on further clinical and mechanistic studies.Fil: Cremonini, Eleonora. University of California; Estados UnidosFil: Fraga, César Guillermo. University of California; Estados Unidos. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Oteiza, Patricia Isabel. University of California; Estados Unido

    “but I am also influenced by no such thing”-The Radical Pietist and Theological Author Johanna Eleonora Petersen

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    Johanna Eleonora von und zu Merlau, verheiratete Petersen, von jeher tief gläubig, veränderte die religiöse Welt des 17. Jahrhunderts. Sie bekannte sich zur Bewegung des Pietismus und vertrat radikale Ansichten, nicht nur im privaten Kreis, sondern als anerkannte und heftig kritisierte theologische Autorin. Ihrem Werk ist eine Studie gewidmet, in der neue Forschungsergebnisse vorgestellt und Leben und Werk dieser bedeutenden Autorin in zeitgenössische Diskurse eingebunden werden.The deeply devout Johanna Eleonora Petersen, whose maiden name was „von und zu Merlau,” changed the religious world of the seventeenth century. She avowed herself to Pietism and held radical views, not only in private but also as an acknowledged and sharply criticized theological author. This study attends to her work. It presents new research results and weaves the life and work of this important author into contemporary discourses
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