Some studies have reported in vitro inactivation of membrane enveloped viruses by Butylated hydroxytoluene (BHT). This study investigates the effect of orally administered BHT on primary infections of Herpes simplex virus (HSV) using rabbit corneas as the assay system. Assigned levels of BHT were incorporated into the diet of New Zealand White rabbits with HSV-1 McKrae strain on the corneal surface of the eyes. The degree of infection was measured by a subjective assay. Rabbits receiving BHT in their diet consistently experienced lower levels of infection. The interpretation of this data is that orally administered BHT can be an effective inhibitor of primary infections by HSV in rabbits.

Controverse qui traverse les années, l’expérimentation animale, en dépit de fortes remises en question par des opposants de plus en plus véhéments, s’inscrit dans un certain immobilisme. A quoi tient cette « stagnation » ? Le substantif est-il d’ailleurs à propos ? La controverse en question ne s’inscrit-elle pas plutôt dans une « dynamique immobile » ? Afin d’étudier cette problématique, la thèse favorise une approche communicationnelle. L’étude se fait en trois temps, tout d’abord par l’analyse du dilemme moral sur lequel repose l’expérimentation animale, ce qui suppose un retour vers un certain nombre de textes philosophiques et éthiques fondamentaux. Puis, l’étude analyse les discours des opposants et des partisans et les raisons d’un difficile, voire impossible dialogue entre les deux camps. Dans cette situation de non-communication, le législateur devient, comme nous le voyons en dernier lieu, un recours dont chaque camp attend une solution… Une solution permettant de sortir de l’immobilisme ? / Throughout the years, despite strong questioning from more and more vehement opponents, the animal testing controversy has come to a standstill. What can explain this « immobility » ? Besides, is the noun accurate ? Is this controversy rather not in line with a « dynamic inertia » ? So as to investigate this issue, communicational approach is put forward.The study is divided into three parts. A first one analyzes the underlying moral dilemma of animal testing, which involves going back to some philosophical sources and ethical principles. Then, the study examines the opponents and supporters speeches as well as the reasons for a difficult and even an impossible dialogue between the two sides. In this situation of non-communication, the legislature is, as we see in the third part, a resort from which each side is expecting a solution... A solution to overcome the inertia ?

Wireless capsule endoscopy (WCE) is a state-of-the-art technology to receive images of human intestine for medical diagnostics. In WCE, the patient ingests a specially designed electronic capsule which has imaging and wireless transmission capabilities inside it. While the capsule travels through the gastrointestinal (GI) tract, it captures images and sends them wirelessly to an outside data logger unit. The data logger stores the image data and then they are transferred to a personal computer (PC) where the images are reconstructed and displayed for diagnosis. The key design challenge in WCE is to reduce the area and power consumption of the capsule while maintaining acceptable image reconstruction. In this research, the unique properties of WCE images are identified by analyzing hundreds of endoscopic images and video frames, and then these properties are used to develop novel and low complexity compression algorithms tailored for capsule endoscopy. The proposed image compressor consists of a new YEF color space converter, lossless prediction coder, customizable chrominance sub-sampler and an efficient Golomb-Rice encoder. The scheme has both lossy and lossless modes and is further customized to work with two lighting modes – conventional white light imaging (WLI) and emerging narrow band imaging (NBI). The average compression ratio achieved using the proposed lossy compression algorithm is 80.4% for WBI and 79.2% for NBI with high reconstruction quality index for both bands. Two surveys have been conducted which show that the reconstructed images have high acceptability among medical imaging doctors and gastroenterologists. The imaging algorithms have been realized in hardware description language (HDL) and their functionalities have been verified in field programmable gate array (FPGA) board. Later it was implemented in a 0.18 μm complementary metal oxide semiconductor (CMOS) technology and the chip was fabricated. Due to the low complexity of the core compressor, it consumes only 43 µW of power and 0.032 mm2 of area. The compressor is designed to work with commercial low-power image sensor that outputs image pixels in raster scan fashion, eliminating the need of significant input buffer memory. To demonstrate the advantage, a prototype of the complete WCE system including an FPGA based electronic capsule, a microcontroller based data logger unit and a Windows based image reconstruction software have been developed. The capsule contains the proposed low complexity image compressor and can generate both lossy and lossless compressed bit-stream. The capsule prototype also supports both white light imaging (WLI) and narrow band imaging (NBI) imaging modes and communicates with the data logger in full duplex fashion, which enables configuring the image size and imaging mode in real time during the examination. The developed data logger is portable and has a high data rate wireless connectivity including Bluetooth, graphical display for real time image viewing with state-of-the-art touch screen technology. The data are logged in micro SD cards and can be transferred to PC or Smartphone using card reader, USB interface, or Bluetooth wireless link. The workstation software can decompress and show the reconstructed images. The images can be navigated, marked, zoomed and can be played as video. Finally, ex-vivo testing of the WCE system has been done in pig's intestine to validate its performance.

Den här uppsatsen är baserad på en enkätundersökning samt intervjuer med gymnasielever angående deras tankar kring djurförsök. Jag har intervjuat studenter från två olika naturbruksgymnasier. Båda har inriktningen djurvård men det är endast en av dem som ger en specialiseringskurs inom forskningsdjur. Min frågeställning är att undersöka om elever som läser kursen i försöksdjurskunskap har en annan inställning än de elever som endast läser djursjukvård. Som resultaten visar så är de eleverna som läser specialiseringskursen mer positiva till både djurförsök och att jobba med försöksdjur. De har också en mer korrekt bild och större vetskap om hur verkligheten ser ut för försöksdjuren. Detta beror till stor del på att de har lärare som är utbildade försöksdjurstekniker och har arbetat länge med försöksdjur inom forskningsvärlden. De elever på gymnasiet där specialiseringskursen inte finns är negativt inställda till djurförsök och anser att djuren torteras och lever under hemska förhållanden. Då de inte ges någon undervisning om forskningsdjur så har deras uppfattning formats genom media, vilket har framgått i enkäterna, till exempel tidningen Djurens rätt. Andra elever ”bara vet” hur verkligheten ser ut för försöksdjuren. De har heller inga kunskaper om regelverket kring forskning och den etiska nämndens uppgift. I uppsatsen ingår även en stor del historia om djurförsök förr i tiden. Det är viktigt att ha kunskap om historien eftersom det ger en bild av hur människans förhållningssätt till djuren har formats och förändrats över tid. / This essay is based on a survey and interviews with high school students regarding their thoughts about animal testing. I have interviewed students from two different high schools inSweden; both are agricultural high schools but only one have got laboratory animal science as a special orientation in the education. The issue on which this essay is based on is whether or not the students who are studying laboratory animal science have a different view on lab animals than students only reading animal healthcare have. As the results show, the students who are studying laboratory animal science are more positive towards both animal testing and also working with lab animals. They also have a more correct view and understanding of the reality of lab animals since they are given an up-to-date education from teachers who has been working in labs and with lab animals. Students not given this special orientation in the subject has a view of animal testing as a very negative thing where animals are tortured and held under cruel circumstances. There negative view of laboratory animal and animal testing is an understanding mostly caused by media, but some of the students “just know” how the reality is for the lab animals. Moreover, the students lack knowledge about the strict regulation that surrounds scientific studies on animals and they do not know about the ethic counsel and its purpose. A large part of history about animal testing in the early days is also included in this essay. I think it is important to have knowledge about our history in order to understand how our relationship towards animals have changed over time.

Les sensibilisants de contact sont des molécules réactives électrophiles qui ont la capacité de modifier des protéines de la peau pour former un antigène. Au delà de ce mécanisme d'hapténisation, le signal de danger induit par les sensibilisants conduisant à l'activation des cellules dendritiques (DC) est un élément déterminant dans l'induction de cellules T spécifiques de l'haptène. Dans le contexte du 7ième amendement à la directive cosmétique européenne, la mise en place d'une batterie de tests in vitro permettant de prédire le potentiel sensibilisant de molécules est indispensable pour l'industrie cosmétique. Tandis que la plupart des études in vitro étudient les signaux de danger induits par les sensibilisants dans des modèles homéostasiques, nous nous sommes intéressés à l'effet des sensibilisants sur la mise en place d'une réponse inflammatoire. Lorsque la lignée U937 est différenciée avec du PMA et stimulée avec du LPS, les facteurs de transcription NF-κB et Nrf2 sont activés et l'acide arachidonique (AA) est métabolisé au travers de la cascade cPLA2 / COX-2. L'ensemble de ces voies activées conduit à la production par les U937 d'un grand nombre de médiateurs inflammatoires (IL-1β, TNF-α, IL-6, IL-10, IL-8, PGE2, PGD2, TxB2). Dans ce modèle, nous avons analysé l'effet de 6 sensibilisants de potentiels variés (DNCB, PPD, HQ, PG, CIN, EUG) et montré que de façon inattendue, tous les sensibilisants étudiés diminuent significativement et de façon spécifique la production de tous les prostanoïdes et en particulier de PGE2 induite par PMA/LPS. Nous avons de plus démontré que selon les sensibilisants, les cibles de cette inhibition au sein de la cascade métabolique de l'AA diffèrent, même si elles se focalisent la plupart du temps (sauf pour le DNCB) sur l'enzyme COX-2 (inhibition de son expression et/ou de son activité). Pour le DNCB, le mécanisme d'inhibition semble plutôt impliquer sa capacité à réagir fortement avec les groupements résidus thiols, ce qui se traduit en particulier par la déplétion du GSH intracellulaire et engendrerait l'inhibition des synthases dépendantes du GSH pour leurs activités. En parallèle de cette étude mécanistique, nous avons appréhendé la problématique du point de vue statistique et vérifié sur un set plus important et diversifié de molécules (160 molécules) que le paramètre « inhibition de PGE2 » pouvait être un bon test de prédiction de l'HSRC. L'étude statistique a permis de déterminer le modèle prédictif du test PGE2 et de mettre en évidence de bonnes performances (78%) par rapport aux prédictions du LLNA. Au-delà, une certaine complémentarité du test PGE2 avec d'autres tests in vitro (MUSST, Nrf2-HTS) a pu être mise en évidence. En conclusion, au travers de cette étude, nous avons pu mettre en évidence de nouvelles propriétés biochimiques des sensibilisants. Même si la signification biologique de la diminution de PGE2 par les sensibilisants de contact demeure complexe d'interprétation, ce paramètre a permis le développement d'un test qui prédit avec de bonnes performances le caractère sensibilisant de molécules et dont la position au sein d'une batterie prédictive d'évaluation de l'allergie de contact reste à être précisée. / Contact sensitizers are defined as reactive molecules (electrophilic) which have the ability to modify skin proteins to form an antigen (hapten). In addition to the haptenation mechanism, danger signals, leading to the activation of dendritic cells, are described to be crucial for the effective induction of an hapten-specific T cell immune response. In the context of the 7th amendment to the Cosmetic Directive, the cosmetic industry is concerned by the challenge of finding non-animal approaches to assess the sensitizing potential of chemicals. While danger signals induced by sensitizers in steady-state conditions have already been analyzed, we chose to investigate the impact of sensitizers on the course of an inflammatory response. For this purpose we used the U937 cell line differentiated with PMA and activated with LPS. In these conditions, cells produce a large amount of inflammatory mediators (IL-β, TNF-α, IL-6, IL-10, IL-8, PGE2, PGD2, TxB2) through the activation of pathways leading to the activation of the transcription factors NF-κB and Nrf2 and through AA metabolism by the cPLA2/COX-2 cascade. Interestingly, we showed that 6 contact sensitizers with various potential (DNCB, PPD, HQ, PG, CIN, EUG) significally and specifically decrease the production of prostanoïds and in particular of PGE2 induced by PMA/LPS. We further demonstrated that there is no unique inhibition profile of the sensitizers even if the majority (except for DNCB) of the effects applies on COX-2 (i.e. inhibition of the expression and/or activity). For DNCB, inhibition mechanism appears to be dependant of its capacity to react with thiols residues and in particular to deplete intracellular glutathione possibly leading to the inactivation of the PG-synthases. In parallel, we assess a statistical analysis on 160 molecules that allow us to define the test parameters (a molecule is a sensitizer if the PGE2 inhibition at 24h is more than 60%) and to calculate the test performance toward LLNA (78%). Moreover we demonstrated that the PGE2 test could be complementary to other already existing in vitro tests like MUSST or Nrf2-HTS. In summary, we add here a new insight into the multiple biochemical effects described so far for sensitizers. Even if the underlying biological relevance remains unclear, the parameter “PGE2 inhibition” is good test for skin sensitization evaluation. Further studies will precise how this parameter could be implemented into an alternative testing strategy for the evaluation of skin sensitization.

<p>  </p> <p>This study investigates consumers’ moral-decision making process when they become aware of brands’ controversial actions. Specifically, this study aims to understand the effects of consumers’ cognitive and affective responses on their moral judgments after learning about the controversy of brands conducting animal testing, which in turn impacts their brand switching intention. The current study also considers consumers’ approach-avoidance conflicts in the moral-decision making process in which consumers confront moral dilemmas. The particular brands’ controversial action of interest for this study is personal care brands’ conducting animal testing on their products and selling animal-tested products because many believe that animal testing is only vital for biomedical research purposes but not for pursuing beauty purposes. This study builds a conceptual model depicting the consumer moral decision-making process based on Rest's (1994) and Schwartz’s (2015) ethical decision-making (EDM) theory and Sirgy’s (1986) self-congruence theory. To test the model, highly valid responses were collected from 454 U.S. nationwide consumers through Amazon’s Mechanical Turk and analyzed by structural equation modeling. The results indicated that: (1) consumers’ affective response (outward-focused emotion) and cognitive response (moral awareness) both provoked their moral incongruence and brand switching intention, (2) consumers’ cognitive response had a negative and significant impact on their moral disengagement, but moral disengagement had a marginal impact on brand switching intentions, (3) consumers’ affective response has a stronger impact on their moral judgment than cognitive, and their affective response can directly lead to brand switching intention, and lastly, (4) moral incongruence and moral disengagement mediated the effects of moral awareness and outward-focused emotion on brand switching intention. Finally, the research findings contribute to the consumer science literature in the area of consumers' moral decision-making process. For practical contributions, this study encourages companies to conduct practice that follows general consumers' moral beliefs and values to avoid losing their loyal customers. </p>

The assessment of teratogenic effects of chemicals is generally performed using in vivo teratogenicity assays e.g., in rats or rabbits. Following the 3R principles, the development of alternative methods is encouraged to reduce the number of animal tests. From this perspective, we have developed an in vitro assay (mDarT) using the zebrafish Danio rerio embryo teratogenicity assay (DarT) combined with an exogenous mammalian metabolic activation system (MAS), able to biotransform proteratogenic compounds. Cyclophosphamide, ethanol, benzo[a]pyrene and thalidomide were used as test materials to assess the efficiency of this assay. Briefly, the zebrafish embryos were co-cultured at 2 hpf (hours post fertilization) with the test material at varying concentrations, mammalian liver microsomes from different species and NADPH for 60 min at 32°C under moderate agitation in Tris buffer. The negative control (test material alone) and the MAS control (MAS alone) were incubated in parallel. For each test group, 20 eggs were used for statistical robustness. Afterwards fish embryos were transferred individually into 24-well plates filled with fish medium for 48 hours at 26°C with a 12 hour-light cycle. Teratogenicity was scored after 24 and 48 hpf using morphological endpoints. The test was considered to be valid if a minimum of 90% of fish eggs developed normally for the two controls (test material alone and MAS alone). For each test material, the experiment was repeated three times with the controls satisfying the validation criteria (≤ 10% impaired embryos). Indeed, no significant teratogenic effects were observed compared to controls in fish embryos exposed to the proteratogens alone (i.e., without metabolic activation) or the MAS alone. In contrast, the four test materials induced significant abnormalities in fish embryos when co-incubated with animal liver microsomes. For cyclophosphamide, ethanol and thalidomide a concentration-response relationship was shown and the qualitative nature of the malformations was similar between fish embryos and humans. Benzo[a]pyrene was demonstrated to be significantly teratogenic in fish embryos in spite of no concentration-response and unspecific teratogenic fingerprints. We conclude that the application of animal liver microsomes will improve and refine the DarT as a predictive and valuable alternative method to screen teratogenic substances.

La Spectroscopie de Résonance Magnétique (SRM) constitue un outil non-invasifunique pour l’exploration biochimique du métabolisme des organismes vivants. Cependant,en raison des champs magnétiques couramment utilisés chez l’homme etle petit animal, la SRM in vivo du proton ne permet pas de quantifier précisémentla concentration de tous les métabolites présents dans le cerveau. La SRM à deuxdimensions spectrales (SRM 2D), technique utilisée en routine en chimie, permetde séparer efficacement les signatures spectrales des métabolites facilitant ainsi leuridentification et leur quantification en termes de concentrations. Les travaux réalisésdans le cadre de cette thèse concernent le développement de méthodes d’acquisitionet de quantification de spectres RMN 2D J-résolus in vivo et sont présentéssuivant deux axes majeurs. Le premier axe concerne les travaux relatifs à la SRM2D J-résolue conventionnelle qui ont fait l’objet du développement d’une séquenceJ-PRESS sur un imageur 7 T pour l’acquisition de spectres 2D sur le cerveau de rat.Les données acquises sont traitées avec une méthode d’analyse spectrale développéeet optimisée spécifiquement pour la quantification de données SRM 2D J-résolues,reposant sur une connaissance a priori et un ajustement numérique dans le domainetemporel. Le second axe concerne les travaux relatifs à la réduction de la duréed’acquisition en SRM 2D avec le développement de techniques basées sur le conceptrécent de RMN ultrarapide. Une nouvelle séquence de SRM 2D J-résolue ultrarapidea été développée et validée sur un imageur 7 T et a permis l’acquisition de spectres2D complets avec une durée d’acquisition de l’ordre de la seconde. / In vivo proton Magnetic Resonance Spectroscopy (MRS) is a powerful tool for metabolicprofiling because this technique is non-invasive and quantitative. However,conventional localized spectroscopy presents important in vivo metabolic informationthrough overlapped spectral signatures greatly affecting the quantification accuracy.Two-dimensional (2D) MRS, originally developed for analytical chemistry,has great potential to unambiguously distinguish metabolites. Therefore, metabolitequantification is improved allowing accurate estimation of their concentrations. Inthis thesis, the research findings are presented under two main headings. The firstline of research focuses on conventional 2D MRS J-resolved. A J-PRESS sequencewas developed allowing the acquisition of in vivo 2D MRS spectra, which were processedby a dedicated quantification method. Experiments were performed on therat brain using a 7 T imaging system and different sampling strategies were evaluated.The quantification method, specifically developed to handle 2D J-resolved MRSdata quantification in time domain, is based on a strong prior-knowledge. However,2D MRS suffers from long acquisition times due to the collection of numerous incrementsin the indirect dimension. Therefore, the second line of research focuseson the reduction of acquisition time using recently developed methods based on theultrafast NMR concept. A new pulse sequence was designed, allowing 3D localizedultrafast 2D J-resolved spectroscopic acquisition on a 7T small animal imaging system. This breakthrough allows the acquisition of a complete 2D spectrum in a singlescan, resulting in acquisition times of a few seconds.

This diploma thesis looks at lobbying as one of the tools for shaping European legislation. Lobbyists are often perceived as carriers of valuable information that make it possible for decision-makers to get expert opinions and perspectives directly from the industry. Lobbyists can therefore make a significant contribution to policy making and to improving European legislation that meets the needs of stakeholders. The main objective of the thesis is to find out in what way and at what stages the interest groups participate and intervene in the EU decision-making process and identify the access points through which they can enter into the legislative process. For the sake of clarity, this research is applied to a particular case of lobbying in the field of animal testing of cosmetics, which has greatly influenced the legal regulation of the area.

The assessment of teratogenic effects of chemicals is generally performed using in vivo teratogenicity assays e.g., in rats or rabbits. Following the 3R principles, the development of alternative methods is encouraged to reduce the number of animal tests. From this perspective, we have developed an in vitro assay (mDarT) using the zebrafish Danio rerio embryo teratogenicity assay (DarT) combined with an exogenous mammalian metabolic activation system (MAS), able to biotransform proteratogenic compounds. Cyclophosphamide, ethanol, benzo[a]pyrene and thalidomide were used as test materials to assess the efficiency of this assay. Briefly, the zebrafish embryos were co-cultured at 2 hpf (hours post fertilization) with the test material at varying concentrations, mammalian liver microsomes from different species and NADPH for 60 min at 32°C under moderate agitation in Tris buffer. The negative control (test material alone) and the MAS control (MAS alone) were incubated in parallel. For each test group, 20 eggs were used for statistical robustness. Afterwards fish embryos were transferred individually into 24-well plates filled with fish medium for 48 hours at 26°C with a 12 hour-light cycle. Teratogenicity was scored after 24 and 48 hpf using morphological endpoints. The test was considered to be valid if a minimum of 90% of fish eggs developed normally for the two controls (test material alone and MAS alone). For each test material, the experiment was repeated three times with the controls satisfying the validation criteria (≤ 10% impaired embryos). Indeed, no significant teratogenic effects were observed compared to controls in fish embryos exposed to the proteratogens alone (i.e., without metabolic activation) or the MAS alone. In contrast, the four test materials induced significant abnormalities in fish embryos when co-incubated with animal liver microsomes. For cyclophosphamide, ethanol and thalidomide a concentration-response relationship was shown and the qualitative nature of the malformations was similar between fish embryos and humans. Benzo[a]pyrene was demonstrated to be significantly teratogenic in fish embryos in spite of no concentration-response and unspecific teratogenic fingerprints. We conclude that the application of animal liver microsomes will improve and refine the DarT as a predictive and valuable alternative method to screen teratogenic substances.