DEVELOPMENTAL ARTICLES REFLECTIONS ON POVERTY AND DISABILITY: A REVIEW OF LITERATURE

ABSTRAC

Perfluorocarbon Particle Size Influences Magnetic Resonance Signal and Immunological Properties of Dendritic Cells

The development of cellular tracking by fluorine (19F) magnetic resonance imaging (MRI) has introduced a number of advantages for following immune cell therapies in vivo. These include improved signal selectivity and a possibility to correlate cells labeled with fluorine-rich particles with conventional anatomic proton (1H) imaging. While the optimization of the cellular labeling method is clearly important, the impact of labeling on cellular dynamics should be kept in mind. We show by 19F MR spectroscopy (MRS) that the efficiency in labeling cells of the murine immune system (dendritic cells) by perfluoro-15-crown-5-ether (PFCE) particles increases with increasing particle size (560>365>245>130 nm). Dendritic cells (DC) are professional antigen presenting cells and with respect to impact of PFCE particles on DC function, we observed that markers of maturation for these cells (CD80, CD86) were also significantly elevated following labeling with larger PFCE particles (560 nm). When labeled with these larger particles that also gave an optimal signal in MRS, DC presented whole antigen more robustly to CD8+ T cells than control cells. Our data suggest that increasing particle size is one important feature for optimizing cell labeling by PFCE particles, but may also present possible pitfalls such as alteration of the immunological status of these cells. Therefore depending on the clinical scenario in which the 19F-labeled cellular vaccines will be applied (cancer, autoimmune disease, transplantation), it will be interesting to monitor the fate of these cells in vivo in the relevant preclinical mouse models

Effects of nano particles on antigen-related airway inflammation in mice

BACKGROUND: Particulate matter (PM) can exacerbate allergic airway diseases. Although health effects of PM with a diameter of less than 100 nm have been focused, few studies have elucidated the correlation between the sizes of particles and aggravation of allergic diseases. We investigated the effects of nano particles with a diameter of 14 nm or 56 nm on antigen-related airway inflammation. METHODS: ICR mice were divided into six experimental groups. Vehicle, two sizes of carbon nano particles, ovalbumin (OVA), and OVA + nano particles were administered intratracheally. Cellular profile of bronchoalveolar lavage (BAL) fluid, lung histology, expression of cytokines, chemokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and immunoglobulin production were studied. RESULTS: Nano particles with a diameter of 14 nm or 56 nm aggravated antigen-related airway inflammation characterized by infiltration of eosinophils, neutrophils, and mononuclear cells, and by an increase in the number of goblet cells in the bronchial epithelium. Nano particles with antigen increased protein levels of interleukin (IL)-5, IL-6, and IL-13, eotaxin, macrophage chemoattractant protein (MCP)-1, and regulated on activation and normal T cells expressed and secreted (RANTES) in the lung as compared with antigen alone. The formation of 8-OHdG, a proper marker of oxidative stress, was moderately induced by nano particles or antigen alone, and was markedly enhanced by antigen plus nano particles as compared with nano particles or antigen alone. The aggravation was more prominent with 14 nm of nano particles than with 56 nm of particles in overall trend. Particles with a diameter of 14 nm exhibited adjuvant activity for total IgE and antigen-specific IgG(1 )and IgE. CONCLUSION: Nano particles can aggravate antigen-related airway inflammation and immunoglobulin production, which is more prominent with smaller particles. The enhancement may be mediated, at least partly, by the increased local expression of IL-5 and eotaxin, and also by the modulated expression of IL-13, RANTES, MCP-1, and IL-6

Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured

Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation

Air pollutant exposure has been linked to a rise in wheezing illnesses. Clinical data highlight that exposure to mainstream tobacco smoke (MS) and environmental tobacco smoke (ETS) as well as exposure to diesel exhaust particles (DEP) could promote allergic sensitization or aggravate symptoms of asthma, suggesting a role for these inhaled pollutants in the pathogenesis of asthma. Mouse models are a valuable tool to study the potential effects of these pollutants in the pathogenesis of asthma, with the opportunity to investigate their impact during processes leading to sensitization, acute inflammation and chronic disease. Mice allow us to perform mechanistic studies and to evaluate the importance of specific cell types in asthma pathogenesis. In this review, the major clinical effects of tobacco smoke and diesel exhaust exposure regarding to asthma development and progression are described. Clinical data are compared with findings from murine models of asthma and inhalable pollutant exposure. Moreover, the potential mechanisms by which both pollutants could aggravate asthma are discussed

Nanotechnology in perspective: summary. Risks for man and the environment

Het Kennis- en Informatiepunt Risico's van Nanotechnologie (KIR-nano) van het RIVM heeft de potentiele risico's van blootstelling van gefabriceerde, vrije, onafbreekbare en onoplosbare nanodeeltjes in kaart gebracht. In dit rapport worden de risico's voor de mens als werknemer, patient en consument behandeld, evenals risico's voor het milieu. Drie toepassingsgebieden zijn daarbij relevant: geneesmiddelen en medische technologie, voedselproductie en consumentenproducten. De huidige stand van zaken van de wetenschap laat zien dat risico's niet uit te sluiten zijn. Er ontbreekt echter nog veel kennis om de risico's even goed in te kunnen schatten als voor 'chemische stoffen niet in nanovorm'. Toch zijn er al vele honderden producten waarin nanomaterialen zijn verwerkt op de markt. Dit vereist op korte termijn veel onderzoek naar de blootstelling en toxiciteit van deze materialen. Helaas is het aantal onderzoeksvragen dusdanig groot en fundamenteel van aard dat het nog jaren zal duren voordat alle informatie is vergaard. KIR-nano adviseert daarom het onderzoek vooral te richten op die vragen die cruciale informatie voor de risicobeoordeling voor mens en milieu bieden. Afhankelijk van het perspectief van werknemer, consument, patient of milieu zijn oplossingsrichtingen gedefinieerd voor het beheersen van de risico's. Informatie die in de streng gereguleerde wereld van medische toepassingen wordt gegenereerd kan met name vanuit methodologisch oogpunt zeer waardevol zijn voor andere toepassingsgebieden, waar de dossiervereisten en dus veelal ook de informatievergaring (veel) beperkter voor zijn. Kernbegrippen voor de komende jaren zijn samen te vatten onder KOKOS: Kennis vergroten en uitwisselen om dubbeling van onderzoek te voorkomen, Oplossingsrichtingen en risicomanagement, Keuzes maken in bijdragen vanuit Nederland aan dit onderzoeksveld, Onderzoek & Ontwikkeling, en Samenwerking bevorderen tussen wet- en regelgevende kaders, wetenschap en bedrijfsleven.The Knowledge and Information Risks Nanotechnology (KIR nano), a Dutch national government-supported observation organization based at RIVM, has provided an overview of the potential risks to both man and the environment of exposure to nanoparticles. The focus is on free, non-degradable and insoluble nanoparticles present in medical applications, food, consumer products and the environment. Scientific data compiled to date demonstrate that negative effects of exposure to nanoparticles cannot be excluded. However, much more information is required to be able to estimate the risks of nanoparticles equally well as those of other (not nano) chemicals. Nevertheless, hundreds of products containing nanomaterials are currently available commercially, a situation which clearly necessitates that the exposure and toxicity of these materials be investigated in the near future. Unfortunately, the research questions to be answered are so numerous that it will take years to compile the relevant data. The advice of the KIR nano is to focus research primarily on those questions that provide information critical to the assessment of risks to man and the environment. Dependent on the perspective - worker, consumer, patient, or the environment - the points of departure can then be defined for controlling (or limiting) the risks. Information (e.g. on methodology) generated in the strongly regulated world of medical applications can be a very valuable asset in other (research) areas of application, where the requirements for dossiers and compiling of pertinent data are not as exacting. Core concepts for the upcoming years include expanding our knowledge of nanoparticles and making this knowledge easily available to avoid any duplication of research, identifying and, where necessary, taking the appropriate risk management measures, choosing the areas of research in which the Netherlands wishes to contribute to this field, supporting Research & Development and promoting collaboration between (semi)government organs/agencies, science and industry.VROMVWSSZ

Nanotechnologie in perspectief. Risico's voor mens en milieu

Summary van dit rapport verschenen onder nummer 601785004Het Kennis- en Informatiepunt Risico's van Nanotechnologie (KIR-nano) van het RIVM heeft de potentiele risico's van blootstelling van gefabriceerde, vrije, onafbreekbare en onoplosbare nanodeeltjes in kaart gebracht. In dit rapport worden de risico's voor de mens als werknemer, patient en consument behandeld, evenals risico's voor het milieu. Drie toepassingsgebieden zijn daarbij relevant: geneesmiddelen en medische technologie, voedselproductie en consumentenproducten. De huidige stand van zaken van de wetenschap laat zien dat risico's niet uit te sluiten zijn. Er ontbreekt echter nog veel kennis om de risico's even goed in te kunnen schatten als voor 'chemische stoffen niet in nanovorm'. Toch zijn er al vele honderden producten waarin nanomaterialen zijn verwerkt op de markt. Dit vereist op korte termijn veel onderzoek naar de blootstelling en toxiciteit van deze materialen. Helaas is het aantal onderzoeksvragen dusdanig groot en fundamenteel van aard dat het nog jaren zal duren voordat alle informatie is vergaard. KIR-nano adviseert daarom het onderzoek vooral te richten op die vragen die cruciale informatie voor de risicobeoordeling voor mens en milieu bieden. Afhankelijk van het perspectief van werknemer, consument, patient of milieu zijn oplossingsrichtingen gedefinieerd voor het beheersen van de risico's. Informatie die in de streng gereguleerde wereld van medische toepassingen wordt gegenereerd kan met name vanuit methodologisch oogpunt zeer waardevol zijn voor andere toepassingsgebieden, waar de dossiervereisten en dus veelal ook de informatievergaring (veel) beperkter voor zijn. Kernbegrippen voor de komende jaren zijn samen te vatten onder KOKOS: Kennis vergroten en uitwisselen om dubbeling van onderzoek te voorkomen, Oplossingsrichtingen en risicomanagement, Keuzes maken in bijdragen vanuit Nederland aan dit onderzoeksveld, Onderzoek & Ontwikkeling, en Samenwerking bevorderen tussen wet- en regelgevende kaders, wetenschap en bedrijfsleven.The Risks of Nanotechnology Knowledge and Information Centre (KIR nano), a Dutch government-supported observation organisation based at RIVM, has provided an overview of the potential risks to both man and the environment of exposure to nanoparticles. The focus is on free, non-degradable and insoluble nanoparticles found in medical applications, food, consumer products and the environment. Scientific data compiled to date demonstrate that adverse effects due to exposure to nanoparticles cannot be ruled out. However, much more information is required to be able to estimate the risks of nanoparticles equally as well as those of other non-nano chemicals. Nevertheless, hundreds of products containing nanomaterials are currently available commercially, a situation which clearly necessitates investigation of the exposure and toxicity of these materials in the near future. unfortunately, the research questions to be answered are so numerous that it will take years to compile the relevant data. KIR nano recommends that research be focused primarily on those questions that provide information critical to the assessment of risks to man and the environment. Depending on the perspective - worker, consumer, patient, or the environment - the starting points can then be defined for controlling or limiting the risks. Information generated in the strictly regulated world of medical applications (e.g., on methodology) could constitute a valuable asset in other areas of research and application, where the data and dossier requirements are not as exacting. Key concepts in the coming years include expanding our knowledge of nanoparticles and making this knowledge readily available to avoid duplication of research; identifying and where necessary taking appropriate risk management measures, deciding on which areas of research the Netherlands wishes to contribute to this field, supporting research & development and promoting cooperation between government bodies and agencies, the scientific community and trade and industry.VROMVWSSZ