The left hemisphere (LH) is accepted as the dominant hemisphere for language processing. There is also evidence confirming the language processing abilities of the right hemisphere (RH), particularly its lexical-semantic processing potential (Chiarello, 1988; Joanette, Goulet, & Hannequin, 1990). The capacity of the RH for language processing is significant to the investigation of language processing following LH lesions. However, the precise neurocognitive mechanisms underlying language processing following lesion remain to be fully elucidated. Subsequently, the overall aim for this thesis is to investigate hemispheric contributions to semantic processing following unilateral lesions, and to explore the significance of the contribution made by the RH. In order to achieve this overall aim, the current thesis firstly explores the hemispheric contributions made to lexical-semantic processing for healthy adults, and then shifts focus to explore the changes in hemispheric processing for participants with unilateral lesions (LH and RH). Comparisons of hemispheric activation between these groups will clarify the underlying hemispheric mechanisms that facilitate language processing following unilateral lesion. This thesis includes four complementary investigations of hemispheric contributions to semantic processing. The first study combined divided visual field (DVF) priming with event-related potentials (ERPs), in order to investigate controlled hemispheric semantic priming for young healthy adults. Two experiments were employed for a between subjects comparison of time-course differences (stimulus onset asynchrony, or SOA, varied between experiments) in hemispheric activation of associated and nonassociated category members. Continuous electroencephalograms were recorded throughout the priming task for each participant, and later analysed with reference to relevant ERP components (N400 and Late Positive Complex). Bilateral N400 priming was revealed for associated category members at both the short and long SOA. There was no significant N400 priming for the nonassociated category member condition. The examination of hemispheric priming of associated and nonassociated category member stimuli over the same time-course was continued in the second study for participants with unilateral LH lesions and matched controls. The second investigation aimed to determine the impact of unilateral LH lesions on controlled hemispheric semantic priming, utilising the DVF priming paradigm with participants following unilateral lesions. This study also aimed to explore associations between hemispheric activation during the online priming task and offline comprehension abilities. Differences in priming were observed between the LH lesion group and the control group, with participants in the LH lesion group requiring the association relationship to elicit priming. Priming also varied for participants as a function of their offline comprehension abilities, with RH priming associated with higher offline scores. The third investigation continued the exploration of hemispheric semantic activation following LH lesion, examining the impact of a LH lesion on interhemispheric control mechanisms, and the modification of hemispheric processing capacities with and without dominant hemisphere control. This investigation again utilised DVF priming with associated and nonassociated category member stimuli, in conjunction with the dual task paradigm. The dual task paradigm is designed to overload one hemisphere’s processing resources in order to remove interhemispheric suppression. Findings indicate that following LH lesions, the RH’s contribution is enhanced under conditions that are designed to overload the LH. The final study shifts from the investigation of participants with LH lesions to the impact of a RH lesion. This exploration of controlled hemispheric semantic priming following RH lesion sought to increase our understanding of the underlying mechanisms for semantic processing following unilateral lesion. The RH’s role in lexical-semantic processing has been documented consistently over approximately the last twenty years, however, there remains limited direct investigation of a RH lesion’s impact on contributions to semantic processing. A single case investigation utilised the same experimental procedure as the second study described. Findings suggest a similar activation pattern between the individual with RH lesion and the control participants, with both exhibiting bilateral activation of the associated and nonassociated category member stimuli. However, a subtle difference was found between the activation of the individual with RH lesion and that of the control group, with the individual with a RH lesion showing increased strategic processing difficulties at the longer SOA. Overall, the current thesis demonstrates the importance of the RH for efficient strategic semantic processing for both healthy adults, and people with unilateral lesions. In addition, this thesis concludes that following a LH lesion, the RH contribution to controlled semantic processing may be associated with successful comprehension, and that RH contributions may be improved with the addition of a secondary task designed to overload LH processing. The present thesis provides evidence to support the use of the DVF priming paradigm in the investigation of hemispheric contributions to semantic processing following unilateral lesion. It is anticipated that these findings will improve the current understanding of the underlying hemispheric contributions to lexical-semantics following a unilateral lesion, and will encourage continuing investigation into the RH’s capacity to impact language recovery.

The left hemisphere (LH) is accepted as the dominant hemisphere for language processing. There is also evidence confirming the language processing abilities of the right hemisphere (RH), particularly its lexical-semantic processing potential (Chiarello, 1988; Joanette, Goulet, & Hannequin, 1990). The capacity of the RH for language processing is significant to the investigation of language processing following LH lesions. However, the precise neurocognitive mechanisms underlying language processing following lesion remain to be fully elucidated. Subsequently, the overall aim for this thesis is to investigate hemispheric contributions to semantic processing following unilateral lesions, and to explore the significance of the contribution made by the RH. In order to achieve this overall aim, the current thesis firstly explores the hemispheric contributions made to lexical-semantic processing for healthy adults, and then shifts focus to explore the changes in hemispheric processing for participants with unilateral lesions (LH and RH). Comparisons of hemispheric activation between these groups will clarify the underlying hemispheric mechanisms that facilitate language processing following unilateral lesion. This thesis includes four complementary investigations of hemispheric contributions to semantic processing. The first study combined divided visual field (DVF) priming with event-related potentials (ERPs), in order to investigate controlled hemispheric semantic priming for young healthy adults. Two experiments were employed for a between subjects comparison of time-course differences (stimulus onset asynchrony, or SOA, varied between experiments) in hemispheric activation of associated and nonassociated category members. Continuous electroencephalograms were recorded throughout the priming task for each participant, and later analysed with reference to relevant ERP components (N400 and Late Positive Complex). Bilateral N400 priming was revealed for associated category members at both the short and long SOA. There was no significant N400 priming for the nonassociated category member condition. The examination of hemispheric priming of associated and nonassociated category member stimuli over the same time-course was continued in the second study for participants with unilateral LH lesions and matched controls. The second investigation aimed to determine the impact of unilateral LH lesions on controlled hemispheric semantic priming, utilising the DVF priming paradigm with participants following unilateral lesions. This study also aimed to explore associations between hemispheric activation during the online priming task and offline comprehension abilities. Differences in priming were observed between the LH lesion group and the control group, with participants in the LH lesion group requiring the association relationship to elicit priming. Priming also varied for participants as a function of their offline comprehension abilities, with RH priming associated with higher offline scores. The third investigation continued the exploration of hemispheric semantic activation following LH lesion, examining the impact of a LH lesion on interhemispheric control mechanisms, and the modification of hemispheric processing capacities with and without dominant hemisphere control. This investigation again utilised DVF priming with associated and nonassociated category member stimuli, in conjunction with the dual task paradigm. The dual task paradigm is designed to overload one hemisphere’s processing resources in order to remove interhemispheric suppression. Findings indicate that following LH lesions, the RH’s contribution is enhanced under conditions that are designed to overload the LH. The final study shifts from the investigation of participants with LH lesions to the impact of a RH lesion. This exploration of controlled hemispheric semantic priming following RH lesion sought to increase our understanding of the underlying mechanisms for semantic processing following unilateral lesion. The RH’s role in lexical-semantic processing has been documented consistently over approximately the last twenty years, however, there remains limited direct investigation of a RH lesion’s impact on contributions to semantic processing. A single case investigation utilised the same experimental procedure as the second study described. Findings suggest a similar activation pattern between the individual with RH lesion and the control participants, with both exhibiting bilateral activation of the associated and nonassociated category member stimuli. However, a subtle difference was found between the activation of the individual with RH lesion and that of the control group, with the individual with a RH lesion showing increased strategic processing difficulties at the longer SOA. Overall, the current thesis demonstrates the importance of the RH for efficient strategic semantic processing for both healthy adults, and people with unilateral lesions. In addition, this thesis concludes that following a LH lesion, the RH contribution to controlled semantic processing may be associated with successful comprehension, and that RH contributions may be improved with the addition of a secondary task designed to overload LH processing. The present thesis provides evidence to support the use of the DVF priming paradigm in the investigation of hemispheric contributions to semantic processing following unilateral lesion. It is anticipated that these findings will improve the current understanding of the underlying hemispheric contributions to lexical-semantics following a unilateral lesion, and will encourage continuing investigation into the RH’s capacity to impact language recovery.

The efficcacy of the treatment of the endodontic-periodontal lesion was evaluated in longitudinal studies, by means through a systematic review. Bibliographic tabulation sources identified electronically by MEDLINE, from 1966 up to March, 26 of 2007 and Cochrane Library, in the same period. As search strategy one used the terms - endodontic-periodontal lesion or endodontic-periodontal lesions or endodontic periodontal lesion or endodontic periodontal lesions or endo-perio lesion or endo-perio lesions or endodontics periodontal lesion or endodontics periodontal lesions - as word-key. The studies had been selected by two copyholders, independent, that also they had determined the criteria of inclusion and exclusion. The search presented 257 related articles, being that, of these, 55 articles were of literature revision, 27 articles became related with prospectives studies, 70 studies was cases reports, 19 studies had been developed in animals and 25 had involved retrospective studies. Absence of longitudinal studies that satisfied the inclusion criteria, with sights to the analysis based on evidences was observed. However, front to applied literature was verified that the success of the treatment of the endodontic-periodontal lesions is related to the brief identification of the etiology, to the control of microbiota present, to the immunological characteristics of the individual, being that one of the strategies and possible prognostic the origin of the infectious process is associated to it. Considering the estimate of success of the clinical success of the endodontic-periodontal lesion an initial microorganisms control in the oral cavity is suggested, followed for the control of endodontical microorganisms and, to follow, the periodontal, for then carrying through the treatment. The immunological system of the individual participates actively of the process as component manager. / Avaliou-se em estudos longitudinais a eficácia do tratamento da lesão endodôntica-periodontal, por meio de revisão sistemática. Utilizou-se de fontes de catalogação bibliográfica identificadas eletronicamente por MEDLINE, a partir de 1966 até 26 de março de 2007 e Cochrane Library, no mesmo período. Como estratégia de busca utilizou-se os termos endodontic-periodontal lesion or endodontic-periodontal lesions or endodontic periodontal lesion or endodontic periodontal lesions or endo-perio lesion or endo-perio lesions or endodontics periodontal lesion or endodontics periodontal lesions como palavras-chave. Os estudos foram selecionados por dois revisores, independentes, que também determinaram os critérios de inclusão e exclusão. A busca apresentou 257 artigos relacionados, sendo que, destes, 55 artigos eram de revisão de literatura, 27 artigos relacionavam-se com estudos prospectivos, 70 estudos eram relatos de casos clínicos, 19 estudos foram desenvolvidos em animais e 25 envolveram estudos retrospectivos. Observou-se ausência de estudos longitudinais que satisfizessem os critérios de inclusão, com vistas à análise baseada em evidências. Contudo, frente à literatura aplicada verificou-se que o sucesso do tratamento das lesões endodônticas-periodontais está relacionado à breve identificação da etiologia, ao controle da microbiota presente, às características imunológicas do indivíduo, sendo que uma das estratégias e o possível prognóstico vincula-se à origem do processo infeccioso (endodôntico ou periodontal). Considerando a estimativa de êxito do sucesso clínico da lesão endodôntica-periodontal sugere-se um controle microbiano inicial na cavidade bucal, seguido pelo controle da microbiota endodôntica e, a seguir, a periodontal, para então realizar o tratamento. O sistema imunológico do indivíduo participa ativamente do processo como componente gerenciador. / Mestre em Odontologia

Inledning: Bröstcancer är en vanlig cancerform hos kvinnor och årligen drabbas 1,5 miljoner kvinnor världen över. Screeningprogram och tidig upptäckt är två faktorer som leder till ökad överlevnad. För kvinnor där en ökad cancerrisk föreligger såsom förhöjd ärftlighet och BRCA-mutation rekommenderar socialstyrelsen att mammografiscreening kompletteras med MR. MR kan komplettera bröstdiagnostik till en mer individanpassad behandling. Syftet: Syftet med denna litteraturstudie var att beskriva hur bröstdiagnostik med magnetkamera (MR) inverkar på den kirurgiska behandlingen av bröstcancer. Metod: En litteraturstudie genomfördes, där 11 kvantitativa artiklar användes för att svara på studiens syfte. Resultat: Preoperativ MR detekterade ytterligare maligna lesioner som inte tidigare var kända vilket medförde en förändrad behandling till mer omfattande kirurgi såsom mastektomi och lumpektomi. MR visade generellt en överskattning av tumörstorlek vid bedömning av tumörutbredning. Utöver den redan diagnostiserade bröstcancern detekterades med MR ytterligare lesioner vilka ej var synliga vid mammografi både i det primära och det kontralaterala bröstet. MR i kombination med biopsi konstaterar maligna lesioner. Slutsats: Fakta tyder på att MR har hög sensitivitet men en lägre specificitet vid detektering av förändringar i bröstvävnaden. Resultatet är ej entydigt och behov finns av ytterligare studier inom ämnet. / Introduction: Breast cancer is a common form of cancer in women, annually, 1.5 million women are affected worldwide. Screening programs and early detection lead to increased survival. In women where there is increased cancer risk with increased heredity and in BRCA mutation, the National Board of Health recommends that mammography screening be supplemented with Magnetic resonance imaging (MRI). MRI can supplement breast diagnosis and can lead to a more personalized treatment. Purpose:The purpose of this literature study was to describe how breast diagnosis with MR affects the surgical treatment of breast cancer. Method: A literature study was conducted, where 11 quantitative articles were used to respond to the purpose of the study.Results: Preoperative MRI detected additional malignant lesions not previously known which resulted in a change in treatment for more extensive surgery such as mastectomy and lumpectomy. MRI generally showed an overestimate of tumor size in the assessment of tumor proliferation. In addition to the already diagnosed breast cancer, MR was detected additional lesions which were not visible in mammography in both the primary and the contralateral breast. MRI in combination with biopsy notes malignant lesions. Conclusion: Facts suggest that MRI has high sensitivity but a lower specificity in detecting changes in the breast tissue. The results are not unambiguous and there is a need for further studies on the subject.

Anlass der vorliegenden Arbeit war die Suche nach einem geeigneten Sehnendefekt-Modell, das die Untersuchung der Wirkung moderner Therapieansätze unter Standardbedingungen ermöglicht. Die Auswertung der Literatur zeigte, dass eine große Anzahl an Sehnendefekt-Modellen mit sehr unterschiedlichen Fragestellungen sowohl an Großtieren, Kleintieren als auch Labortieren eingesetzt wurde. In der vorliegenden Arbeit wurden bekannte Sehnendefekt-Modelle mit besonderem Augenmerk auf die verwendete Methodik und das damit induzierte Schadmuster untersucht. Die umfassende Literaturauswertung mit präziser pathomorphologischer Charakterisierung der Defekte diente als entscheidende Grundlage für die Entwicklung des eigenen Tiermodells. Beim hier vorgestellten Schafmodell handelt es sich um ein Core Lesion- Modell. Es simuliert die am häufigsten beim Pferd auftretende Sehnenerkrankung und bietet die Möglichkeit der direkten intraläsionalen Injektion eines Therapeutikums. Die Core Lesion stellt ein abgeschlossenes Kompartiment dar, so dass keine Trägermaterialien nötig sind, um ein appliziertes Therapeutikum am Wirkort zu binden. Verschiedene chirurgische Zugänge und Zielsehnen wurden beim Schafmodell untersucht. Als geeignet für ein Core Lesion- Modell erwiesen sich beim Schaf die tiefe Beugesehne distal des Karpalgelenks sowie die oberflächliche Beugesehne im Bereich des Tendo calcaneus communis. Für die Induktion der Läsion wurden in Anlehnung an die von LITTLE und SCHRAMME (2006) bzw. SCHRAMME et al. (2010a) beim Pferd gezeigte Methodik unterschiedliche chirurgische Instrumente verwendet. Dabei wurden der Einsatz einer Knochenmark-Extraktionsnadel sowie verschiedene manuell oder elektrisch betriebene arthroskopische Klingen und Fräsköpfe hinsichtlich ihrer Verwendbarkeit sowie des durch sie verursachten Schadmusters miteinander verglichen. Ein manueller Instrumenteneinsatz führte zu deutlich milderen Schadmustern. Dabei kam es durch die Verwendung des Stiletts einer Knochenmark-Extraktionsnadel in einigen Bereichen zu scharfen Faserdurchtrennungen, in anderen Bereichen wurden die Kollagenfasern nur stumpf auseinander gedehnt. Der Einsatz arthroskopischer Klingen und Fräsköpfe beim Schafmodell ist nur eingeschränkt möglich. Durch die geringe Sehnengröße stehen nur sehr wenige Instrumente mit einem entsprechend kleinen Durchmesser zur Verfügung. Ein Round Burr konnte unter experimentellen Bedingungen eingesetzt werden und führte zu einer hochgradigen Schädigung des kompletten Sehnenquerschnitts. Dabei wurden die Fasern aus ihrer ursprünglichen Orientierung heraus gerissen, zumeist aber nicht vom umgebenden Gewebe abgetrennt. Ein Synovial Resector führte hingegen zu einer scharfen Faserdurchtrennung und dadurch zu einem deutlich abgegrenzten Defektbereich. Weitere Einzelheiten wie die resultierende Einblutung und das Einwandern verschiedener Entzündungszell-Spezies müssen in-vivo untersucht werden, um eine klare Empfehlung für den Einsatz der verschiedenen Instrumente formulieren zu können. Die Auswertung der vorhandenen Sehnendefekt-Modelle sowie die eigenen Ergebnisse führten zu dem Schluss, dass eine Kombination verschiedener Methoden sinnvoll sein könnte. Die Arbeit beschreibt ein sicheres, praktikables Großtiermodell für die Simulation von Core Lesions. Das Modell kann zunächst im Tierversuch eingesetzt werden, um die nach Defektinduktion ablaufenden pathophysiologischen Prozesse zu charakterisieren. Dann steht mit dem Schafmodell ein zeitgemäßes Modell für die Untersuchung verschiedener Therapiekonzepte zur Verfügung, das für die Pferdemedizin eingesetzt werden kann, sich aber auch für Untersuchungen mit humanmedizinischem Hintergrund vielversprechend zeigt. Das Modell stellt damit ein wichtiges Bindeglied zwischen Grundlagenforschung und dem klinischen Einsatz moderner Therapiekonzepte dar.

No description available.

Inledning:Oral cancer är ett allvarligt tillstånd med hög dödlighet, särskilt vid sen diagnostisering. Brasilien är ett av de länder i världen som har högst prevalens och dödlighet i oral cancer och det är den femte vanligaste cancerformen I landet. Ett hjälpmedel för tidig diagnostisering är önskvärd.Syfte:Att utvärdera skillnaden i diagnostisk tillförlitlighet mellan konventionell oral undersökning och användning av multispektralt ljus (Identafi®) som en metod för tidig upptäckt av potentiellt maligna och maligna lesioner i munslemhinnan i en brasiliansk befolkning.Material och metod:Screening av en befolkning med förhöjd risk för att utveckla oral cancer i Goiânia, Goiás, Brasilien, för att upptäcka potentiellt maligna (PML) eller maligna lesioner (ML). Patienter med misstänkta PML eller ML upptäckta under screeningen undersöktes med multispektralt ljus (Identafi®). Tre oberoende observatörer genomförde bedömning med Identafi® och slutgiltig beslut avseende PML/ML togs i konsensus. Biopsier användes som diagnostisk referensstandard. Interobservatörs överensstämmelse beräknades som procentuell överensstämmelse och kappa-värde (κ).Resultat:Undersökning med Identafi® genererade tolv biopsier. Resultaten blev tre sant positiva, fem falskt positiva, två sant negativa och noll falskt negativa. Sensitiviteten beräknades till 0,29. Specificiteten var inte möjlig att beräkna, då det inte fanns några falska negativa resultat. Interobservatörs överensstämmelse för par av observatörer varierade mellan 78-86% och κ-värden mellan 0,46-0,60.Slutsats:Slutsatsen är att multispektralt ljus, Identafi® inte har inga fördelar jämfört med konventionell klinisk undersökning i fråga om diagnostisk träffsäkerhet för PML eller ML. Dock kan det vara till hjälp för en tandläkare eller oral kirurg som stöd i sitt beslutsfattande. Det kan också hjälpa kirurgen att ta en biopsi från det mest misstänkta delen av lesionen. Det finns inte tillräckligt publicerade studier som tyder på att Identafi® kan skilja mellan normal slemhinna och PML eller ML och denna studie bekräftar detta. Användning av Identafi® som ett hjälpmedel vid screening och undersökning för PML eller ML behöver utredas ytterligare, men baserat på denna studie kan Identafi® inte rekommenderas. / Introduction: Oral cancer is a severe condition with high mortality rate, in particular if diagnosed late. Brazil is one of the countries in the world with high prevalence and mortality from oral cancer and it is the fifth most common cancer there. An aid in early detection of oral cancer as an adjunct to health promotion is desirable.Purpose:The aim of this study was to evaluate the diagnostic accuracy of conventional oral examination and the use of multi spectral light (Identafi®) as an approach for early detection of potentially malignant or malignant lesions in the oral mucosa in a Brazilian population.Material and method:Screening of high-risk population in Goiania, Goias, Brazil, for oral potentially malignant lesions (PML) or malignant lesions (ML) as a selection phase. Patients collected from the screening were examined with multi spectral light (Identafi®) to evaluate diagnostic accuracy. Three observers independently assessed all lesions with Identafi® and the final decision if a lesion was present was taken in consensus. Inter observer agreement was calculated as overall agreement and as kappa value (κ). Biopsies were used as diagnostic reference standard.Results:Identafi® generated, from twelve biopsies, three true positive, five false positive, two true negative and zero false negative. Sensitivity was calculated to 0.29 and specificity was not possible to calculate since there were no false negative results.Inter observer agreement for the use of Identafi® was calculated as overall agreement and as kappa value (κ). The overall agreement for the three pairs of observers varied between 78-86% and κ-values between 0.46 and 0.60.Conclusion:The conclusion of this study is that Identafi® does not have any benefits over conventional oral examination in diagnostic accuracy for potentially malignant or malignant lesions in the oral mucosa. It might, however, be an aid for a dentists or oral surgeons that are unsure whether to take a biopsy or not. It can also aid the surgeon when taking a biopsy to take the most suspicious part of the lesion. There are not enough published evidence that Identafi® can discriminate between normal mucosa and PML or ML, and this study confirms previous results. The use of Identafi® as an aid in screening and examination for PML or ML needs further investigation.

Red blood cells (RBCs) are vital for oxygen delivery to tissues and constitute the vast majority of all cells in blood. After leaving the red bone marrow as mature cells, RBCs have a lifespan of approximately 120 days before they are removed from the circulation by macrophages, mainly in the spleen and liver. RBC transfusion is a common therapy in modern healthcare. Major surgery, numerous cancer treatments and other, often lifesaving, interventions would be unthinkable without available blood supply. For this reason, hospitals store donated RBCs in blood banks. The metabolic and structural changes that occur during prolonged storage of RBCs (the storage lesion) have been studied in detail in vitro and include oxidative stress, a reduction in glycolysis, increased membrane rigidity and shedding of microparticles from the RBC membrane. Stored RBCs share several features of senescent RBCs, but also with RBCs undergoing an apoptotic-like process called eryptosis. A consequence of the storage lesion is the fact that as much as 25% of stored RBCs could be rapidly removed from the circulation within 24 hours after transfusion. The mechanisms behind this rapid macrophage-mediated recognition and removal of stored RBCs, and its immunological consequences, remain largely unknown. Therefore, the aims of this thesis were to investigate if cryopreserved human RBCs induced an inflammatory response following autologous transfusion into healthy volunteers, and to further understand the mechanisms behind macrophage recognition of stored RBCs in vitro and in vivo. Autologous transfusion of two units of cryopreserved RBCs into healthy human recipients was found to be associated with an increased extravascular RBC elimination already at 2 hours after transfusion. However, there were no signs of an increased production of any of the investigated pro-inflammatory cytokines, indicating that an increase in the destruction of RBCs per se did not induce an inflammatory response. Eryptosis is a form of induced RBC death associated with an increased cytoplasmic Ca2+ uptake. We found that a subset of human RBCs increased their Ca2+ permeability during prolonged storage at +4°C. Using a murine model, to further understand how RBCs with an increased Ca2+ permeability were eliminated by phagocytic cells in the spleen, it was found that such RBCs were taken up by marginal zone macrophages and dendritic cells (DCs) in a manner distinct from that of naturally senescent RBCs. The DC population particularly efficient in this process expressed CD207 and are known for their ability to promote immunological tolerance. Eryptotic cell uptake was not regulated by the phagocytosis-inhibitory protein CD47 on the RBCs. To investigate how RBCs damaged during liquid storage are recognized and taken up by macrophages, a model to store and transfuse murine RBCs was developed. This storage model generated murine RBCs with several characteristics similar to that of stored human RBCs (i.e. loss of ATP, formation of RBC microparticles and rapid clearance of up to 35% of the RBCs during the first 24 h after transfusion). In vitro phagocytosis of human as well as murine stored RBCs was serum dependent and could be inhibited by blocking class A scavenger receptors using fucoidan or dextran sulphate. In conclusion, the findings of this thesis contribute to further understanding how changes inflicted to RBCs during storage direct the fate of these cells in their interaction with cells of the immune system after transfusion. The observation of an increased Ca2+ permeability of stored RBCs, and the possible recognition of such cells by tolerance-promoting DCs, in combination with the findings that class A scavenger receptors and serum factors may mediate recognition of stored RBCs, may result in novel new directions of research within the field of transfusion medicine.

Ocular pathology is one of the main health problems worldwide. The number of people with retinopathy symptoms has increased considerably in recent years. Early adequate treatment has demonstrated to be effective to avoid the loss of the vision. The analysis of fundus images is a non intrusive option for periodical retinal screening. Different models designed for the analysis of retinal images are based on supervised methods, which require of hand labelled images and processing time as part of the training stage. On the other hand most of the methods have been designed under the basis of specific characteristics of the retinal images (e.g. field of view, resolution). This compromises its performance to a reduce group of retinal image with similar features. For these reasons an unsupervised model for the analysis of retinal image is required, a model that can work without human supervision or interaction. And that is able to perform on retinal images with different characteristics. In this research, we have worked on the development of this type of model. The system locates the eye structures (e.g. optic disc and blood vessels) as first step. Later, these structures are masked out from the retinal image in order to create a clear field to perform the lesion detection. We have selected the Graph Cut technique as a base to design the retinal structures segmentation methods. This selection allows incorporating prior knowledge to constraint the searching for the optimal segmentation. Different link weight assignments were formulated in order to attend the specific needs of the retinal structures (e.g. shape). This research project has put to work together the fields of image processing and ophthalmology to create a novel system that contribute significantly to the state of the art in medical image analysis. This new knowledge provides a new alternative to address the analysis of medical images and opens a new panorama for researchers exploring this research area.

La migration des cellules souches / progénitrices neurales (CSPN) dans le cerveau adulte est cruciale pour la réparation cérébrale. Reeline (Rln) est une protéine de la matrice extracellulaire, régulant le positionnement des neurones pendant la croticogénèse. Nous révélons un rôle nouveau de Rln chez l'adulte. In vitro, Rln est chémocinétique mais pas chémoattractante. In vivo, Rln induit le détachement et la dispersion des CSNP de la zone sousventriculaire (SVZ) hors du courant rostral de migration (RMS) où elles sont sinon confinées. Rln potentialise le recrutement spontané des CSPN vers les lésions démyélinisantes où un tiers deviennent oligodendrocytaires. L'expression endogène de Rln est stimulée après lésion. Les animaux sans voie de signalisation Rln ont un recrutement réduit des CSPN vers les lésions.Ces résultats révèlent que Rln est un arbitre clef de la migration post-lésionnelle des CSPN et que permettre au CSPN de sortir du RMS est une stratégie thérapeutique prometteuse. / Neural stem/ progenitor cell (NSPC) migration in the adult brain is crucial for brain repair. Reelin (Rln) is an extracellular matrix protein regulating neuron positioning during coricogenesis. We reveal new roles of Rln in adult NSPC migration. In vitro, Rln promotes detachment, is chemokinetic but not chemoattractant. After Rln ectopic overexpression in the healthly brain, subventricular zone (SVZ) NSPC detach from the rostal migratory stream (RMS) in which they are normally restricted, and disperse in adjacent fiber tracts. Rln over-expression potentiates spontaneous cell recruitment to demyelinated lesion and one third of the NSPC recruited adopt an oligodendrocytic phenotype. Rln expression is spontaneously upregulated after lesion, and disruption of its signaling pathway results in reduced NSPC recruitment toward lesion. Our study reveals that Rln is a key player of post-lesional NSPC migration and that allowing NSPC to escape from RMS is a promising therapeutic approach