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Search Results: 1 - 10 of 394 matches for " Saskia Braber "
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Inflammatory changes in the airways of mice caused by cigarette smoke exposure are only partially reversed after smoking cessation
Saskia Braber, Paul AJ Henricks, Frans P Nijkamp, Aletta D Kraneveld, Gert Folkerts
Respiratory Research , 2010, DOI: 10.1186/1465-9921-11-99
Abstract: The severity of airway remodeling and inflammation was studied by analyzing alveolar enlargement, heart hypertrophy, inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung tissue and by determining the cytokine and chemokine profiles in the BALF of A/J mice exposed to cigarette smoke for 20 weeks and 8 weeks after smoking cessation.The alveolar enlargement and right ventricle heart hypertrophy found in smoke-exposed mice remained unchanged after smoking cessation. Although the neutrophilic inflammation in the BALF of cigarette smoke-exposed animals was reduced after smoking cessation, a sustained inflammation in the lung tissue was observed. The elevated cytokine (IL-1α and TNF-α) and chemokine (CCL2 and CCL3) levels in the BALF of smoke-exposed mice returned to basal levels after smoking cessation, while the increased IL-12 levels did not return to its basal level. The cigarette smoke-enhanced VEGF levels did not significantly change after smoking cessation. Moreover, IL-10 levels were reduced in the BALF of smoke-exposed mice and these levels were still significantly decreased after smoking cessation compared to the control animals.The inflammatory changes in the airways caused by cigarette smoke exposure were only partially reversed after smoking cessation. Although smoking cessation should be the first step in reducing the progression of lung emphysema, additional medication could be provided to tackle the sustained airway inflammation.There are currently more than 1.3 billion tobacco smokers worldwide according to the World Health Organization (WHO) [1]. Cigarette smoke contains more than 4000 hazardous chemical compounds, of which 200 are highly toxic [2]. It is generally accepted that cigarette smoking is the most important risk factor for the development and progression of chronic obstructive pulmonary disease (COPD) and accounts for about 80% of COPD cases [3,4]. COPD, a term referring to two lung diseases: chronic bronchitis and emphysema,
Cigarette smoke induces β2-integrin-dependent neutrophil migration across human endothelium
Saskia A Overbeek, Saskia Braber, Paul A J Henricks, Marije Kleinjan, Vera M Kamp, Niki A Georgiou, Johan Garssen, Aletta D Kraneveld, Gert Folkerts
Respiratory Research , 2011, DOI: 10.1186/1465-9921-12-75
Abstract: Utilizing freshly isolated human PMNs, the effect of cigarette smoke on migration and β2-integrin activation and function in neutrophilic transmigration was studied. In this report, we demonstrated that cigarette smoke extract (CSE) dose dependently induced migration of neutrophils in vitro. Moreover, CSE promoted neutrophil adherence to fibrinogen. Using functional blocking antibodies against CD11b and CD18, it was demonstrated that Mac-1 (CD11b/CD18) is responsible for the cigarette smoke-induced firm adhesion of neutrophils to fibrinogen. Furthermore, neutrophils transmigrated through endothelium by cigarette smoke due to the activation of β2-integrins, since pre-incubation of neutrophils with functional blocking antibodies against CD11b and CD18 attenuated this transmigration.This is the first study to describe that cigarette smoke extract induces a direct migratory effect on neutrophils and that CSE is an activator of β2-integrins on the cell surface. Blocking this activation of β2-integrins might be an important target in cigarette smoke induced neutrophilic diseases.Neutrophils play a pivotal role in pulmonary inflammatory diseases, such as chronic obstructive pulmonary disease (COPD). COPD is a progressive disease, which is characterized by two major pathological processes, namely bronchitis and emphysema. The neutrophils accumulate in the affected tissues and contribute to the chronic inflammatory reaction, eventually leading to lung destruction [1,2]. It is generally accepted that cigarette smoking is the most important risk factor for the development of COPD. The WHO estimated that 73% of COPD mortality is related to smoking [3]. However, not only COPD patients have increased neutrophil counts in bronchoalveolar lavage fluid (BALF) and sputum [4-7]; increased neutrophil numbers are also observed in sputum of smokers without respiratory problems [5,8].To migrate from the blood stream to the lung, neutrophils use a specific set of adhesion and chemokine rec
Targeting Prolyl Endopeptidase with Valproic Acid as a Potential Modulator of Neutrophilic Inflammation
Mojtaba Abdul Roda, Mariam Sadik, Amit Gaggar, Matthew T. Hardison, Michael J. Jablonsky, Saskia Braber, James Edwin Blalock, Frank A. Redegeld, Gert Folkerts, Patricia L. Jackson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097594
Abstract: A novel neutrophil chemoattractant derived from collagen, proline-glycine-proline (PGP), has been recently characterized in chronic obstructive pulmonary disease (COPD). This peptide is derived via the proteolytic activity of matrix metalloproteases (MMP's)-8/9 and PE, enzymes produced by neutrophils and present in COPD serum and sputum. Valproic acid (VPA) is an inhibitor of PE and could possibly have an effect on the severity of chronic inflammation. Here the interaction site of VPA to PE and the resulting effect on the secondary structure of PE is investigated. Also, the potential inhibition of PGP-generation by VPA was examined in vitro and in vivo to improve our understanding of the biological role of VPA. UV- visible, fluorescence spectroscopy, CD and NMR were used to determine kinetic information and structural interactions between VPA and PE. In vitro, PGP generation was significantly inhibited by VPA. In vivo, VPA significantly reduced cigarette-smoke induced neutrophil influx. Investigating the molecular interaction between VPA and PE showed that VPA modified the secondary structure of PE, making substrate binding at the catalytic side of PE impossible. Revealing the molecular interaction VPA to PE may lead to a better understanding of the involvement of PE and PGP in inflammatory conditions. In addition, the model of VPA interaction with PE suggests that PE inhibitors have a great potential to serve as therapeutics in inflammatory disorders.
Cigarette Smoke-Induced Collagen Destruction; Key to Chronic Neutrophilic Airway Inflammation?
Saskia A. Overbeek, Saskia Braber, Pim J. Koelink, Paul A. J. Henricks, Esmaeil Mortaz, Adele T. LoTam Loi, Patricia L. Jackson, Johan Garssen, Gerry T. M. Wagenaar, Wim Timens, Leo Koenderman, J. Edwin Blalock, Aletta D. Kraneveld, Gert Folkerts
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055612
Abstract: Background Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD). In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline-Glycine-Proline (N-ac-PGP). The generation of this tripeptide is mediated by a multistep pathway involving matrix metalloproteases (MMPs) 8 and 9 and prolyl endopeptidase (PE). Here we investigated whether cigarette smoke extract (CSE) stimulates human PMNs to breakdown whole matrix collagen leading to the generation of the chemotactic collagen fragment N-ac-PGP. Methodology/Principal Findings Incubating PMNs with CSE led to the release of chemo-attractant CXCL8 and proteases MMP8 and MMP9. PMNs constitutively expressed PE activity as well as PE protein. Incubating CSE-primed PMNs with collagen resulted in collagen breakdown and in N-ac-PGP generation. Incubation of PMNs with the tripeptide N-ac-PGP resulted in the release of CXCL8, MMP8 and MMP9. Moreover, we tested whether PMNs from COPD patients are different from PMNs from healthy donors. Here we show that the intracellular basal PE activity of PMNs from COPD patients increased 25-fold compared to PMNs from healthy donors. Immunohistological staining of human lung tissue for PE showed that besides neutrophils, macrophages and epithelial cells express PE. Conclusions This study indicates that neutrophils activated by cigarette smoke extract can breakdown collagen into N-ac-PGP and that this collagen fragment itself can activate neutrophils, which may lead in vivo to a self-propagating cycle of neutrophil infiltration, chronic inflammation and lung emphysema. MMP-, PE- or PGP-inhibitors can serve as an attractive therapeutic target and may open new avenues towards effective treatment of COPD.
Influence of the Multispecies Probiotic Ecologic® BARRIER on Parameters of Intestinal Barrier Function  [PDF]
Saskia Van Hemert, Geline Ormel
Food and Nutrition Sciences (FNS) , 2014, DOI: 10.4236/fns.2014.518187
Abstract: The intestinal epithelium is a single cell layer that forms the largest and most important barrier against the external environment. A proper functioning of the intestinal barrier is essential for maintaining optimal health. A disrupted intestinal barrier function has been associated with the development of autoimmune and inflammatory diseases. Probiotics are live microorganisms that confer a health benefit to the host and have been associated with prevention of diseases such as antibiotic-associated diarrhea, irritable bowel syndrome and inflammatory bowel disease. Probiotics can improve and restore the intestinal barrier function in diverse ways and effects are thought to be species- and even strain-specific. With this research the influence of probiotic bacteria in Ecologic? BARRIER on parameters of intestinal barrier function was investigated. The results show that each bacterial strain in Ecologic?BARRIER is in vitro capable to improve the epithelial barrier in diverse ways.
Localizando ciudades en circuitos globales
Sassen,Saskia;
EURE (Santiago) , 2003, DOI: 10.4067/S0250-71612003008800001
Abstract: there have long been cross-border economic processes. in the last hundred years, the inter-state system came to provide the dominant organizational form cross-border flows, with national states as its key actors. this condition has changed dramatically over the last decade and more, as a result of privatization, deregulation, the opening up of national economies to foreign firms and the growing participation of national economic actors in global markets. in this context, we see a re-scaling of what are the strategic territories that articulate the new system. the organizational architecture for cross-border flows that results from these re-scaling and articulations increasingly diverges from that of the inter-state system. my central effort here is to contribute to empirical and theoretical specification of this organizational architecture. among the features examined here are the combination of centralization and dispersal trends, the disproportionate concentration of value and transactions in the north atlantic, the role of cities in an increasingly digitized global economy, especially as illustrated by the growth of finance and specialized services, and the impact of information technologies on urban economies
El reposicionamiento de las ciudades y regiones urbanas en una economía global: ampliando las opciones de políticas y gobernanza
Sassen,Saskia;
EURE (Santiago) , 2007, DOI: 10.4067/S0250-71612007000300002
Abstract: this paper addresses two critical urban and regional policy issues. one concerns actual shifts in the scales, spaces and contents of economic activity focusing in three types of critical processes: the ongoing formation of global cities; the novel trend towards the formation of mega-regions and the expansion of cross-border flows connecting cities at diverse levels of the urban hierarchy the second concerns the needed shifis in our interpretations and policy frameworks to adjust to these novel trends and maximize their benefits and distributive potential, examining some of the key challenges these developments generate for globalising cities and urban areas, from economic to social
Ciudades en la economía global: enfoques teóricos y metodológicos
Sassen,Saskia;
EURE (Santiago) , 1998, DOI: 10.4067/S0250-71611998007100001
Abstract: in relation to the question: what explains the new or sudden expansion of the role played by a specific city within the world economy since the beginning of the eighties?, the article takes on two perspectives. on the one hand, it analyses the impact derived from the increase in globalization of economic actitivy -something which has broadened the scale and complexity of economic transactions- and, on the other, it investigates the growth of the impact of services within the organisation of the economy. bearing in mind that the key process, from the point of view of urban economies, is the growing demand for services by companies in all industries, and the fact that cities are preferred sites by such services production, be it on a global, national or regional level, the article examines in detail the main components of the new discourse that has emerged from the research on world or global cities
Cityness. Roaming thoughts about making and experiencing cityness
Sassen,Saskia;
Ex aequo , 2010,
Abstract: the text problematizes the term ?urbanity?, as used in the west, and proposes the notion of ?cityness? as a tool and as an intersection of differences which may open to something new, namely, other ways of appropriation of public spaces.
Una Sociología De La Globalización
Sassen,Saskia;
Análisis Político , 2007,
Abstract: in its introduction, the text presents the basis for a sociology of globalization at affi rming that such a phenomenon is comprehensible not only in terms of interdependency and formation of exclusively global institutions but in regard to something within what is national. after overcoming a methodological nationalism it becomes possible to approach a growing number of cases of localization of what is global and others of denationalization of what is national which, meanwhile, opens a wide range of research possibilities in social sciences. then, a study of global cities as a convenient space to test theoretical assumptions of such a sociology is undertaken since, in those cities, a new transnational geography serving as a space for new transnational politics emerges.
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