Body image among Chinese-Australian and European-Australian men

Little is known about the body image concerns of non-European men living in Australia. In this research, Chinese-Australians demonstrated an "holistic" body image that included body shape, height, clothing and hairstyling concerns. Contrastingly, European-Australians separated muscularity concerns from general appearance considerations. Chinese-Australians utilised both Asian and Western internalisation/appearance comparison targets. The portfolio aims to critically evaluate the clinical utility of Evidence Based Practice (EBP). Four case studies analyse the practical advantages and disadvantages of EBP.

A novel nanoplatform for oral delivery of anti-cancer biomacromolecules

Oral administration of bio–macromolecules is an uphill task and the challenges from varying pH and enzymatic activity are difficult to overcome. In this regard, nanotechnology promises the new hope and offers advantages such as controlled release, target specific delivery, combinatorial therapy and many more. In this study, we demonstrate the formulation of a novel alginate enclosed, chitosan coated ceramic, anti cancer nano carrier (ACSC NC). These NC were loaded with multi functional anti cancer bovine lactoferrin (Lf), a natural milk based protein, for improvement of intestinal absorption, in order to develop a novel platform to carry anti cancer protein and/or peptides for oral therapy. Here we demonstrate the size, morphology, internalisation and release profiles of the nanoparticles (NC) under varying pH as perceived in human digestive system. We further determine the uptake of these particles by colon cancer cell lines by measuring the endocytosis and transcytosis of the NC. These NC can be used for future targeted protein/peptide or nucleic acid based drug delivery to treat difficult diseases including cancer.

A hermeneutic study of pattern mining as a knowledge creation process : exploring multimedia design practices

In this paper, we discuss a special case of knowledge creation via pattern mining that was studied using a hermeneutic approach. The reported study explores the nature of knowledge creation by domain practitioners who do not communicate directly. The focus of this paper extends the traditional view of a knowledge creation process beyond organisational boundaries. The proposed knowledge creation framework explains the facilitated process of knowledge creation by its qualification, combination, socialisation, externalisation, internalisation and introspection, thus allowing the transformation of individual experience and knowledge into formalised shareable domain knowledge.

Environmental sustainability change management in SMEs : learning from sustainability champions

This study identifies the change management processes involved in undertaking environmental sustainability (ES) initiatives within Small and Medium Size Enterprises (SMEs) and relate these to the main attributes of learning organisations. Using case study techniques, the study draws from the change management experiences of a sample of 12 ES champions in different industries. The findings suggest that the ES champions experience four distinct change management stages in undertaking ES initiatives; namely the design, internalise, implement and evaluate stages. Each stage is also found to relate strongly with a number of key characteristics of learning organisations. Overall, the findings suggest that SMEs with strong learning organisation attributes are more likely to be successful in implementing and managing ES change initiatives. The implications of the findings are also discussed.

Physiological metal uptake by Nostoc punctiforme

Trace metals are required for many cellular processes. The acquisition of trace elements from the environment includes a rapid adsorption of metals to the cell surface, followed by a slower internalization. We investigated the uptake of the trace elements Co²⁺, Cu²⁺, Mn²⁺, Ni²⁺, and Zn²⁺ and the non-essential divalent cation Cd²⁺ in the cyanobacterium Nostoc punctiforme. For each metal, a dose response study based on cell viability showed that the highest non-toxic concentrations were: 0.5 μM Cd²⁺, 2 μM Co²⁺, 0.5 μM Cu²⁺, 500 μM Mn²⁺, 1 μM Ni²⁺, and 18 μM Zn²⁺. Cells exposed to these non-toxic concentrations with combinations of Zn²⁺ and Cd²⁺, Zn²⁺ and Co²⁺, Zn²⁺ and Cu²⁺ or Zn²⁺ and Ni²⁺, had reduced growth in comparison to controls. Cells exposed to metal combinations with the addition of 500 μM Mn²⁺ showed similar growth compared to the untreated controls. Metal levels were measured after one and 72 h for whole cells and absorbed (EDTA-resistant) fractions and used to calculate differential uptake rates for each metal. The differences in binding and internalisation between different metals indicate different uptake processes exist for each metal. For each metal, competitive uptake experiments using ⁶⁵Zn showed that after 72 h of exposure Zn²⁺ uptake was reduced by most metals particularly 0.5 μM Cd²⁺, while 2 μM Co²⁺ increased Zn²⁺ uptake. This study demonstrates that N. punctiforme discriminates between different metals and favourably substitutes their uptake to avoid the toxic effects of particular metals.

A re-examination of the benefits of exercise for state body satisfaction: Considerationof individual difference factors

Although the link between exercise and body image is well documented, the considerable inter-individual variability in this relationship has been largely ignored. Therefore, the aim of the present study was to test the contributions of key body image and exercise-related moderators (age, body mass index (BMI), exercise frequency, trait body dissatisfaction, internalisation of appearance standards, and body surveillance tendencies) in predicting variability in the exercise-body satisfaction relationship. Thirty-seven undergraduate women completed a questionnaire containing the above trait-based measures and then carried a Personal Digital Assistant (PDA) for a 7-day period. Participants were instructed to use the PDA to self-report their state body satisfaction immediately following an exercise session and also when the PDA signalled at each of six random intervals throughout the day. Multilevel modelling revealed a bi-directional relationship between exercise and state body satisfaction. Moreover, post-exercise increases in state body satisfaction were strongest for individuals who were younger and engaged in regular exercise, and weakest for individuals with high BMI and/or the tendency to compare their appearance with others. These findings highlight potential limits on the efficacy of exercise-based therapy for body image disturbances.

Making visible the invisible act of doping

This paper describes the construction of the visual space of surveillance by the global anti-doping apparatus, it is a space inhabited daily by professional cyclists. Two principal mechanisms of this apparatus will be discussed—the Whereabouts System and the Biological Passport; in order to illustrate how this space is constructed and how it visualises the invisible act of doping. These mechanisms act to supervise and govern the professional cyclist and work to classify them as either clean or dirty in terms of the use of prohibited doping substances or methods. Contrary to the analysis of liberal anti-doping scholars such as Hanstad, Loland and Møller this paper argues that Foucault’s Panopticon paradigm is a useful tool for the analysis of this apparatus. The Whereabouts System and Biological Passport are the instruments by which the anti-doping apparatus intensifies the construction of the space of surveillance in professional sport. This space of surveillance not only locates and makes visible the physical location of each individual cyclist, but it also makes visible their internal bodily functions, in this case the composition and the fluctuations of the composition of their blood. In making the cyclist visible the instruments do not allow the cause of doping, or the event of doping to be known or observed. Rather what they do is cast the body in terms of abnormalities of time, place or blood. In the case of an abnormality of the cyclist’s blood, the cause itself cannot be identified with any certainty, all that is made visible is a suggestion, or a probability, that doping may have occurred. The ultimate effects are twofold—an internalisation and continual monitoring of one’s self as well as by the authorities, and a radical change in the nature and the definition of the offence of doping. No longer is it positive evidence of doping that is punishable, but what becomes punishable is an abnormality, in the cyclist’s location, or their body, which suggests a probability that the invisible act of doping may have occurred. In the course of this process accepted manners of proving an offence by the use of scientific evidence and expert commentary are transformed. The Whereabouts System and the Biological Passport open up a new manner in which the invisible can be visualised. Through the discourse and the attendant commentary of the expert a new alliance between doping and the law is constructed. The result is a redistribution of the way in which the law visualises and treats the symptoms (the signifier) and the signified act of doping. The Whereabouts System and Biological Passport are the instruments by which the anti-doping apparatus intensifies the construction of the space of surveillance in professional sport. This space of surveillance not only locates and makes visible the physical location of each individual cyclist, but it also makes visible their internal bodily functions, in this case the composition and the fluctuations of the composition of their blood. In making the cyclist visible the instruments do not allow the cause of doping, or the event of doping to be known or observed. Rather what they do is cast the body in terms of abnormalities of time, place or blood. In the case of an abnormality of the cyclists’s blood, the cause itself cannot be identified with any certainty, all that is made visible is a suggestion, or a probability, that doping may have occurred. The ultimate effects are twofold—an internalisation and continual monitoring of one’s self as well as by the authorities, and a radical change in the nature and the definition of the offence of doping. No longer is it positive evidence of doping that is punishable, but what becomes punishable is an abnormality, in the cyclist’s location, or their body, which suggests a probability that the invisible act of doping may have occurred. In the course of this process accepted manners of proving an offence by the use of scientific evidence and expert commentary are transformed. The Whereabouts System and the Biological Passport open up a new manner in which the invisible can be visualised. Through the discourse and the attendant commentary of the expert a new alliance between doping and the law is constructed. The result is a redistribution of the way in which the law visualises and treats the symptoms (the signifier) and the signified act of doping.

hZip1 (hSLC39A1) regulates zinc homoeostasis in gut epithelial cells

Zinc is an essential trace element required for enzyme catalysis, gene regulation and signal transduction. Zinc absorption takes place in the small intestine, however, the mechanisms by which cells accumulate zinc are not entirely clear. Zip1 (SLC39A1) is a predicted transmembrane protein that is postulated, but not conclusively proven to mediate zinc influx in gut cells. The aim of this study was to investigate a role for hZip1 in mediating zinc uptake in human enterocytes. Both hZip1 mRNA and protein were detected in human intestinal tissue. In non-differentiated Caco-2 human gut cells, hZip1 was partially localised to the endoplasmic reticulum. In contrast, in differentiated Caco-2 cells cultured in extracellular matrix, the hZip1 protein was located in proximity to the apical microvilli. Lack of surface antibody binding and internalisation indicated that hZip1 was not present on the plasma membrane. Functional studies to establish a role for hZip1 in cellular zinc accumulation were carried out using 65Zn. In Caco-2 cells harbouring an hZip1 overexpression construct, cellular zinc accumulation was enhanced relative to the control. Conversely, Caco-2 cells with an hZip1 siRNA construct showed reduced zinc accumulation. In summary, we show that the Caco-2 cell differentiation endorses targeting of hZip1 to a region near the apical domain. Given the absence of hZip1 at the apical plasma membrane, we propose that hZip1 may act as an intracellular sensor to regulate zinc homoeostasis in human gut cells.

Controlling the philosophical imaginary: reading Pierre Hadot with Luiz Costa Lima

This essay proffers a critical complement to Luiz Costa Lima's claims concerning the nature, history, and control of the imagination in Western culture. Accepting the wide scope of Costa Lima's critical claim about the socio-political control of imaginative literature in Western history, we claim that Pierre Hadot's work on philosophy as a bios in the ancient West cautions us lest we position philosophy in this history as always and necessarily an agency of control. At different times, philosophy has rather stood as an ally in practicing and promoting forms of criticity, and the playful, creative, and transformative envisaging of alternative ways of experiencing the world Costa Lima theoretically celebrates in literary fiction. Any critique of philosophy as always opposed to the critical imagination can only stand, we have argued, relative to philosophy as conceived on what Hadot suggests is but one, albeit the now hegemonic model: namely, as a body of systematic rational discourses, including discourses about the literary, poetics, and imaginary. What this vision of philosophy misses, Hadot shows, is how the ancient conception of philosophy (which survives in figures like Montaigne, Nietzsche, and Goethe) as a way of life promoted distinctly literary, aesthetic, and imaginative practices; first, to assist in the existential internalisation of the schools' ideas; secondly, to envisage in the sage and utopias edifying counterfactuals to help students critically reimagine accepted norms; and thirdly, in the conception of a transformed way of living and perceiving ‘according to nature’, whose parameters of autonomy and pleasurable contemplation of the singularity of the present experiences anticipate the experiences delineated in modern aesthetic theory.

Locating cosmopolitanism within academic mobility

Intensified academic mobility is an enticing platform for examining the emerging manifestations of cosmopolitanism in expanding intercultural encounters. Cosmopolitanism calls for a dialogue between cultures and for reciprocal appropriation and internalisation of cultures within one’s own culture. This paper endeavours to locate empirical evidence on evolving cosmopolitanism in everyday intercultural interactions and academic experiences. It is guided by the methodological applications of cosmopolitanism and the way cosmopolitanism is redefining the sociological frame of reference. This paper presents discussion and empirical testing of three defining features of cosmopolitanism according to Beck (2002): globality, plurality and civility. Mirroring these guiding principles, this research attempted to identify and analyse cosmopolitan values and dispositions in everyday intercultural encounters, discourses, situations and experiences. This paper presented an argument that cosmopolitan values and dispositions tend to create mutually beneficial conditions for intercultural inclusion and academic mobility provides a fertile ground for their current and future exploration. 

Aí eu era Antônio Brasil: contribuições de situações didáticas com conhecimentos históricos para a construção da identidade pessoal da criança na educação infantil

L'objectif de cette étude est de comprendre la relation entre les situations didactiques faisant appel aux connaissances historiques et la construction de l'identité personnelle pour les enfants dans l'éducation de la petite enfance. Sa question centrale se demande si les connaissances sont offrent des contributions à la construction de l'identité personnelle par les enfants de la petite enfance. Se distingue, lui aussi, entend contribuer à élargir le débat sur l'enseignement et l'apprentissage des thèmes historiques dans l'éducation des enfants, et permettre un dialogue avec d'autres enseignants dans cette étape de l'éducation. Ont été analysés par des principes théoriques et méthodologiques de qualité et a assumé les orientations méthodologiques de la recherche collaborative. Il a été constaté que la systématisation des situations didactiques impliquant la connaissance historique dans l'éducation de la petite enfance contribue à la construction de l'identité personnelle de l'enfant. Ceci, pour prendre possession de ces connaissances, ils recueillent des renseignements qui permet le plus large éventail de relations, afin de comparer les pratiques culturelles de son temps avec des pratiques à d'autres moments. Ainsi orientée, l'enfant cherche à raconter son histoire avec le thème historique à laquelle elle a eu accès, d'organiser et de construire des réponses des explications sur leur environnement et de lui-même. Tout cela montre à la réalisation que le processus d'internalisation des connaissances historiques de l'enfant est construit comme un sujet et, par conséquent, cette connaissance peut être conçu comme un médiateur dans la formation de l'identité personnelle

A Federação das Indústrias do Estado de São Paulo e as inflexões do capital na década de 1990

Pós-graduação em Ciências Sociais - FFC

Transcriptional regulation of human mu-opioid receptor gene: functional characterization of activating and inhibitory transcription factors

The organization of the nervous and immune systems is characterized by obvious differences and striking parallels. Both systems need to relay information across very short and very long distances. The nervous system communicates over both long and short ranges primarily by means of more or less hardwired intercellular connections, consisting of axons, dendrites, and synapses. Longrange communication in the immune system occurs mainly via the ordered and guided migration of immune cells and systemically acting soluble factors such as antibodies, cytokines, and chemokines. Its short-range communication either is mediated by locally acting soluble factors or transpires during direct cell–cell contact across specialized areas called “immunological synapses” (Kirschensteiner et al., 2003). These parallels in intercellular communication are complemented by a complex array of factors that induce cell growth and differentiation: these factors in the immune system are called cytokines; in the nervous system, they are called neurotrophic factors. Neither the cytokines nor the neurotrophic factors appear to be completely exclusive to either system (Neumann et al., 2002). In particular, mounting evidence indicates that some of the most potent members of the neurotrophin family, for example, nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF), act on or are produced by immune cells (Kerschensteiner et al., 1999) There are, however, other neurotrophic factors, for example the insulin-like growth factor-1 (IGF-1), that can behave similarly (Kermer et al., 2000). These factors may allow the two systems to “cross-talk” and eventually may provide a molecular explanation for the reports that inflammation after central nervous system (CNS) injury has beneficial effects (Moalem et al., 1999). In order to shed some more light on such a cross-talk, therefore, transcription factors modulating mu-opioid receptor (MOPr) expression in neurons and immune cells are here investigated. More precisely, I focused my attention on IGF-I modulation of MOPr in neurons and T-cell receptor induction of MOPr expression in T-lymphocytes. Three different opioid receptors [mu (MOPr), delta (DOPr), and kappa (KOPr)] belonging to the G-protein coupled receptor super-family have been cloned. They are activated by structurallyrelated exogenous opioids or endogenous opioid peptides, and contribute to the regulation of several functions including pain transmission, respiration, cardiac and gastrointestinal functions, and immune response (Zollner and Stein 2007). MOPr is expressed mainly in the central nervous system where it regulates morphine-induced analgesia, tolerance and dependence (Mayer and Hollt 2006). Recently, induction of MOPr expression in different immune cells induced by cytokines has been reported (Kraus et al., 2001; Kraus et al., 2003). The human mu-opioid receptor gene (OPRM1) promoter is of the TATA-less type and has clusters of potential binding sites for different transcription factors (Law et al. 2004). Several studies, primarily focused on the upstream region of the OPRM1 promoter, have investigated transcriptional regulation of MOPr expression. Presently, however, it is still not completely clear how positive and negative transcription regulators cooperatively coordinate cellor tissue-specific transcription of the OPRM1 gene, and how specific growth factors influence its expression. IGF-I and its receptors are widely distributed throughout the nervous system during development, and their involvement in neurogenesis has been extensively investigated (Arsenijevic et al. 1998; van Golen and Feldman 2000). As previously mentioned, such neurotrophic factors can be also produced and/or act on immune cells (Kerschenseteiner et al., 2003). Most of the physiologic effects of IGF-I are mediated by the type I IGF surface receptor which, after ligand binding-induced autophosphorylation, associates with specific adaptor proteins and activates different second messengers (Bondy and Cheng 2004). These include: phosphatidylinositol 3-kinase, mitogen-activated protein kinase (Vincent and Feldman 2002; Di Toro et al. 2005) and members of the Janus kinase (JAK)/STAT3 signalling pathway (Zong et al. 2000; Yadav et al. 2005). REST plays a complex role in neuronal cells by differentially repressing target gene expression (Lunyak et al. 2004; Coulson 2005; Ballas and Mandel 2005). REST expression decreases during neurogenesis, but has been detected in the adult rat brain (Palm et al. 1998) and is up-regulated in response to global ischemia (Calderone et al. 2003) and induction of epilepsy (Spencer et al. 2006). Thus, the REST concentration seems to influence its function and the expression of neuronal genes, and may have different effects in embryonic and differentiated neurons (Su et al. 2004; Sun et al. 2005). In a previous study, REST was elevated during the early stages of neural induction by IGF-I in neuroblastoma cells. REST may contribute to the down-regulation of genes not yet required by the differentiation program, but its expression decreases after five days of treatment to allow for the acquisition of neural phenotypes. Di Toro et al. proposed a model in which the extent of neurite outgrowth in differentiating neuroblastoma cells was affected by the disappearance of REST (Di Toro et al. 2005). The human mu-opioid receptor gene (OPRM1) promoter contains a DNA sequence binding the repressor element 1 silencing transcription factor (REST) that is implicated in transcriptional repression. Therefore, in the fist part of this thesis, I investigated whether insulin-like growth factor I (IGF-I), which affects various aspects of neuronal induction and maturation, regulates OPRM1 transcription in neuronal cells in the context of the potential influence of REST. A series of OPRM1-luciferase promoter/reporter constructs were transfected into two neuronal cell models, neuroblastoma-derived SH-SY5Y cells and PC12 cells. In the former, endogenous levels of human mu-opioid receptor (hMOPr) mRNA were evaluated by real-time PCR. IGF-I upregulated OPRM1 transcription in: PC12 cells lacking REST, in SH-SY5Y cells transfected with constructs deficient in the REST DNA binding element, or when REST was down-regulated in retinoic acid-differentiated cells. IGF-I activates the signal transducer and activator of transcription-3 (STAT3) signaling pathway and this transcription factor, binding to the STAT1/3 DNA element located in the promoter, increases OPRM1 transcription. T-cell receptor (TCR) recognizes peptide antigens displayed in the context of the major histocompatibility complex (MHC) and gives rise to a potent as well as branched intracellular signalling that convert naïve T-cells in mature effectors, thus significantly contributing to the genesis of a specific immune response. In the second part of my work I exposed wild type Jurkat CD4+ T-cells to a mixture of CD3 and CD28 antigens in order to fully activate TCR and study whether its signalling influence OPRM1 expression. Results were that TCR engagement determined a significant induction of OPRM1 expression through the activation of transcription factors AP-1, NF-kB and NFAT. Eventually, I investigated MOPr turnover once it has been expressed on T-cells outer membrane. It turned out that DAMGO induced MOPr internalisation and recycling, whereas morphine did not. Overall, from the data collected in this thesis we can conclude that that a reduction in REST is a critical switch enabling IGF-I to up-regulate human MOPr, helping these findings clarify how human MOPr expression is regulated in neuronal cells, and that TCR engagement up-regulates OPRM1 transcription in T-cells. My results that neurotrophic factors a and TCR engagement, as well as it is reported for cytokines, seem to up-regulate OPRM1 in both neurons and immune cells suggest an important role for MOPr as a molecular bridge between neurons and immune cells; therefore, MOPr could play a key role in the cross-talk between immune system and nervous system and in particular in the balance between pro-inflammatory and pro-nociceptive stimuli and analgesic and neuroprotective effects.

Einfluss verschiedener nanopartikulärer Systeme auf die zelluläre Aufnahme und Zytotoxizität

Die vorliegende Dissertation untersucht Nanopartikel und Nanokapseln aus verschiedenen Materialien mit verschiedenen Modifikationen für einen zielgerichteten Medikamententransport (Drug Targeting). Obwohl bisher zahlreiche Nanopartikel und -kapseln synthetisiert wurden, besteht nach wie vor hinsichtlich der zellulären Verträglichkeit, Biokompatibilität und Aufnahme kein allumfassendes Verständnis. Mit Hilfe der in dieser Arbeit vorgestellten Untersuchungen und Ergebnissen soll ein Beitrag zur Schließung dieser Lücke geleistet werden.rnIm Rahmen der vorliegenden Dissertation wurde der Einfluss der Herstellungsmaterialien PS, PLLA, PMMA, Biomakromoleküle (BSA, DNA), ggf. stabilisiert durch HPMA-LMA-Copolymere und neu-synthetisierte Surfmere, der Formmodifikationen Streckung und Kristallisierung, der Oberflächenmodifikationen mittels verschiedener Tenside und PEG auf die zelluläre Aufnahme und Verträglichkeit hin untersucht.rnZusammenfassend lässt sich die Aussage treffen, dass zahlreiche Materialien zur Herstellung von Trägersystemen geeignet sind und sich als biokompatibel und nicht-zytotoxisch erwiesen haben, sich jedoch stark hinsichtlich der Aufnahmeeffizienz in verschiedene Zelllinien unterscheiden. rnIm ersten Abschnitt (Kapitel 5.1) wurden in der ersten und zweiten Untersuchung auf allgemeine Parameter, die die Aufnahme von Nanopartikeln beeinflussen, eingegangen. Hier wurde der Einfluss des Alters von PLLA-Partikeln auf die zelluläre Aufnahme und Toxizität untersucht. Es konnte gezeigt werden, dass mit zunehmender Materialalterung die zelluläre Aufnahme abnimmt. Eine Zytotoxizität konnte nicht gezeigt werden.rnWeiterhin wurde der Einfluss des FCS-Gehalts des Zell-Mediums auf die zelluläre Aufnahme von PMMA-Partikeln untersucht. Es konnte gezeigt werden, dass mit einer steigenden FCS-Konzentration eine Abnahme der zellulären Aufnahme von PMMA-Partikeln einhergeht. Die höchste zelluläre Aufnahme konnte bei einem FCS-Gehalt des Zellmediums von 0,05% verzeichnet werden. rnIm zweiten Abschnitt (Kapitel 5.2) wurde die Stabilisierung von Nanopartikeln mittels neusynthetisierter Tenside und deren Einfluss auf die Zelle-Nanopartikel-Interaktionen untersucht. Dazu wurde zum einen die Oberflächenfunktionalisierung von Nanopartikeln mit Hilfe neu-synthetisierter „Surfmere“ und deren Einfluss auf die zelluläre Aufnahme und Toxizität untersucht. Die hergestellten Surfmere bewirken gleichzeitig eine Stabilisierung und Funktionalisierung der Nanopartikeloberfläche mit Phosphonatgruppen. Hier wurden kovalente „Surfmer“ stabilisierte Nanopartikel mit Tensid- (SDP) stabilisierten Nanopartikeln verglichen. Zudem wurden dialysierte Nanopartikel mit nicht-dialysierten verglichen. Bezüglich der zellulären Aufnahme konnte für die mittels Dialyse gereinigten Nanopartikel eine gute Aufnahme ohne Unterschiede zwischen den kovalent und nicht-kovalent Phosphonat-funktionalisierten Partikeln beobachtet werden. Die ungereinigten, SDP-stabilisierte, nicht-kovalent gebundene Nanopartikel zeigten hingegen eine bis zu 30% stärkere Aufnahme in die HeLa-Zellen und hMSCs.rnWeiterhin der Einsatz von mit HPMA-LMA-Copolymeren stabilisierte Polystyrol- und PLLA-Partikel, die den Einsatz von Tensiden während des Miniemulsionsprozesses überflüssig machen, untersucht. Auch hier konnte keine Zytotoxizität nachgewiesen werden. Die Aufnahme in HeLa-Zellen scheint mehr von der Größe der Nanopartikel als vom verwendeten Material und in hMSCs mehr von den Oberflächeneigenschaften der Nanopartikel abzuhängen.rnIm dritten Abschnitt (Kapitel 5.3) wird auf die Möglichkeit der Formmodifikation von Polystyrol-Partikeln und deren Einfluss auf die Nanopartikel-Zelle-Interaktionen eingegangen. Es geht dabei um die Aufnahme und Zytotoxizität von verstreckten (elongierten) Polystyrol-Partikeln im Vergleich zu sphärischen Nanopartikeln, sowie die Aufnahme und Zytotoxizität von kristallinen Polystyrol-Partikeln in verschiedene Zelllinien. Bei den verstreckten Partikeln nimmt die Aufnahme-Effizienz in HeLa-Zellen und hMSCs mit zunehmender Verstreckung ab. Eine Zytotoxizität konnte für keinen der erwähnten Nanopartikel nachgewiesen werden. Bei den Polystyrol-Partikeln unterschiedlicher Taktizität zeigen die kristallierten Polystyrol-Partikel eine geringfügig besser Aufnahme-Rate als die nicht-kristallierten Polystyrol-Partikel. Dabei zeigen die nach dem Herstellungsprozess mittels der Lösemittelverdampfungstechnik der wässrigen Phase entnommenen Partikel eine bessere Aufnahme als die nach der Verdampfung des Chloroforms verfügbaren Partikel. Insgesamt konnte jedoch für alle Polystyrol-Partikel trotz der unterschiedlichen Taktizitäten nach der Aufnahme in HeLa-Zellen und hMSCs mittels Durchflusszytometrie hohe Fluoreszenz-Intensitäten verzeichnet werden. Setzt man hohe Fluoreszenz-Intensitäten bei in Zellen aufgenommenen Partikeln mit guten Aufnahmeraten gleich, sind die hier dargestellten Aufnahmeraten als sehr gut zu bezeichnen. rnAuf Nanosysteme mit einer reduzierten zellulären Aufnahme wird im letzten Abschnitt (Kapitel 5.4) eingegangen. Dabei wird zum einen die unterschiedliche Oberflächenmodifikation von Polystyrol-Partikeln mit dem Co-Monomer PEG-MA und den Tensiden SDS und Lutensol AT50 untersucht. Von PEG-MA wurden zudem verschiedene Molekulargewichte (Mn=300 g•mol-1 und Mn=2080 g•mol-1) und verschiedene Konzentrationen (1,5%, 5%, 10%) eingesetzt. Ein Teil der Partikel wurde mit SDS und der andere Teil mit Lutensol AT50 hergestellt. In einem weiteren Schritt wurde das jeweilig gegenteilige Tensid (statt SDS Lutensol AT50 und umgekehrt) eingesetzt, um zu überprüfen, ob sich der zuvor beobachtete Effekt umkehren lässt. Anschließend wurde ein erst mit SDS stabilisierter Nanopartikel (BR01) mit verschiedenen Lutensol AT50-Anteilen (5%, 10%, 25%, 50%, 100%) redispergiert. Die effizienteste Aufnahme zeigte der unmodifizierte, mit SDS stabilisierte Nanopartikel BR01, die niedrigste der ebenfalls unmodifizierte, mit Lutensol AT50 stabilisierte Nanopartikel BR02. Eine steigende Konzentration des PEG-MA Mn=300 g•mol-1 hemmt die Aufnahme von mit SDS stabilisierten Partikeln konstant. Für PEG-MA Mn=2080 g•mol-1 konnte hingegen kein Einfluss nachgewiesen werden. Für die mit Lutensol AT50 stabilisierten Partikel konnte kein Einfluss von PEG-MA nachgewiesen werden. Daraus resultiert, dass der Einsatz von physikalisch adsorbiertem Lutensol AT50 die zelluläre Aufnahme effektiver hemmt als der Einsatz von kovalent gebundenem PEG-MA unterschiedlicher Kettenlänge.rnDer Einsatz von mit Biomakromolekülen hergestellten Nanokapseln, die mit zwei verschiedenen Tensiden (SDS und Lutensol AT50) stabilisiert wurden, wurde im Weiteren näher untersucht. Bei den mit SDS stabilisierten Kapseln erwiesen sich die mit ssDNA hergestellten Kapseln BN-54 und BN-55 als leicht toxisch für die HeLa-Zellen. Dagegen sind alle eingesetzten, mit Lutensol AT50 redispergierten Nanokapseln sowohl für HeLa-Zellen als auch für hMSCs zytotoxisch. Hier ist die toxische Wirkung auf das nicht-ionische Tensid Lutensol AT50 zurückzuführen. Eine zelluläre Aufnahme konnte für keine mit Biomakromolekülen hergestellten Nanokapsel nachgewiesen werden.rnDen Abschluss der Untersuchungen bildet die vergleichende Analyse der in dieser Arbeit mit dem Fluoreszenzfarbstoff PMI versehenen Partikeln hinsichtlich deren Aufnahme in HeLa-Zellen und hMSCs und deren zytotoxische Auswirkungen. In der vergleichenden Analyse werden die zuvor vorgestellten Ergebnisse für PMI-Partikeln nochmal im Kontext betrachtet. Dabei erwies sich sowohl für die HeLa-Zellen als auch für die hMSCs, dass die meisten Partikel eine geringe bis keine zelluläre Aufnahme zeigen. Eine gute Aufnahme konnte nur für wenige Nanopartikel (vor allem für die kristallinen Nanopartikel) verzeichnet werden. Eine Korrelation zwischen der Aufnahmeeffizienz und der Zytotoxizität konnte nicht nachgewiesen werden. rn