L' étude réalisée s'est portée sur la détermination de l’âge à partir d’investigations sur l’alvéolyse humaine.Le manque de fiabilité de l’attache épithéliale comme indicateur d’âge et l’absence de corrélation de la translucidité dentinaire sur dents entières ou coupées ont démontré l'intérêt d'un nouveau modèle odontologique d'estimation de l'âge. Nous avons, pour cela, , recruté une série importante de scanners (500)à visée implantaire assortis d’un questionnaire médico-administratif administré en face à face. Une base équilibrée en terme de sex-ratio et de classes d’âge a été constituée avec comme critère d’inclusion des secteurs dentés et observables. La deuxième phase a consisté à pratiquer des mesures biométriques de la hauteur de perte d’os alvéolaire par rapport au référent classique que constitue la jonction émail Cément. A partir des données relevées, et ajustées sur les variables individuelles et comportementales recueillies dans le questionnaire, nous avons établi une corrélation avec la variable continue, l’âge. Nous avons pu proposer un modèle d’estimation de l’âge alternatif à celui de la méthode odontologique de Lamendin avec une fiabilité identique mais applicable sur des classes d’âges de 25 à 60 ans.Cette méthode a été validée par une étude comparative de trois indicateurs d'erreurs et la formule optimisée par la méthode Bootstrap. Les modèles ont été, ensuite, appliqués sur une série de crânes anciens complets (32) et sur une population contemporaine (50). Enfin, nous avons ouvert la perspective ,à partir du même protocole, d'estimation de l'alvéolyse à partir de l'âge ajusté ou non sur les différentes variables retenues dans l'étude principale. / The study carried out concerned to the determination of the age from investigations on the human alveolar bone loss. The lack of reliability of the tie epithelial as indicator of age and the absence of correlation of the transparency of the dentin on whole or cut teeth demonstrated the interest of a new odontological model of estimation of the age. We have, for it, recruited an important series of scanners (500) for implantological treatment matched by a medical administrative questionnaire administered opposite to face. A base balanced in term of sex-ratio and age groups was established with as criterion of inclusion of the toothed and observable sectors. The second phase consisted in practicing biometric measures of the height of loss of alveolar bone with regard to the classic referent that the junction enamel Cement establishes .From the data, and adjusted on the individual and behavioral variables collected in the questionnaire, we established a correlation with the continuous variable, the age. We were able to propose a model of estimation of the age in that of the odontological method of Lamendin with an identical but applicable reliability on age groups from 25 to 60 years. This method was validated by a comparative study of three indicators of errors and the formula optimized by the Bootstrap method. The models were, then, applied to a series of ancient complete skulls (32) and to a contemporary population (50). Finally, we opened the prospect, from the same protocol, from the estimation of the alveolar bone loss from the adjusted age or not on the various variables held) in the main study.

L'échinococcose alvéolaire (EA) humaine est une maladie parasitaire, rare et grave, due à un cestode parasite, Echinococcus multilocularis, dont le cycle sauvage, en France, passe généralement par le renard (hôte définitif) et le campagnol (hôte intermédiaire). La moitié des cas européens recensés sont regroupés en France, et se concentrent surtout dans les zones rurales de Franche-Comté et Lorraine. Malgré de nombreuses études, la répartition des malades et les facteurs de susceptibilité ou de protection de certaines personnes face à la maladie sont encore mal connus.Depuis 1997, il existe un réseau de surveillance épidémiologique de l’échinococcose alvéolaire humaine, qui a constitué un registre des cas français d’EA, collectant des données sur la pathologie mais aussi sur les lieux et habitudes de vie des patients. L’objectif de ce travail était :- d’étudier les facteurs de risque de l’EA humaine en France, en particulier les facteurs comportementaux impliqués,- d’étudier l’impact du climat et de l’environnement sur l’incidence de la maladie- de déterminer les principaux facteurs utiles pour la prévention de l'infection, ainsi que les populations-cibles pour d'éventuelles campagnes de prévention. / Human alveolar echinococcois (AE), a rare and serious parasitic disease, is caused by a cestode, Echinococcus multilocularis. In France, foxes and water voles are the main hosts (respectively definitive and intermediate). Half of the European human cases are French, mainly living in rural areas in Franche-Comté and Lorraine. Despite numerous studies, human distribution and factors affecting human vulnerability remain poorly understood.Created in 1997, the French epidemiological surveillance network for human AE collects data on the disease characteristics and also on lifelong locations and behaviors of the patients.The objectives of this study were:- to determine individual risk factors for human AE in France, and especially at-risk behaviors,- to study the role of the environment on human AE incidence,- to identify key messages and target populations for potential prevention campaigns.

Magister Scientiae Dentium - MSc(Dent) / Autologous bone grafting in conjunction with dental implant therapy is a well-accepted procedure in oral and maxillofacial rehabilitation. A variety of intraoral donor sites, such as the mandibular symphysis, the mandibular ramus and the maxillary tuberosity have been used in oral and maxillofacial reconstruction. However these sites are associated with complications. In order to reduce these complications, the anterior palate has been proposed as a potential donor site. However, the scientific literature in this regard is sparse, and larger studies are required to investigate the clinical potential of this proposed site. Aim: To determine the volume and density of available bone in the anterior palate that may be used for bone harvesting using cone-beam computed tomography (CBCT) in a select South African population. Materials and methods: One hundred previously acquired CBCT scans taken at the Diagnostic and Radiology Department of Tygerberg Oral Health Centre were analyzed for the required data. These were all acquired from a single CBCT machine (Newtom VGI®, Verona, Italy). The study sample included 52 females and 48 males ranging from ages 20 years to 80 years. The CBCT scans were divided into 3 different age groups. The first age group was between the ages of 20 and 39 years, the second age group was from 40 to 59 years and the third age group was ≥ 60 years. The volume and density of the anterior palate of the different age groups were analyzed using specific criterion. CBCT specific software (Simplant Pro Crystal®) Dentsply implants, Mannheim, Germany was used to standardize the data collection. All data was stored in a Microsoft Excel spreadsheet (Microsoft Corporation, Washington, USA). Results: The mean volume of the anterior palate in this study was 2.11 ± 0.55 cm3, with a minimum volume of 1.04 cm3 and a maximum volume of 3.82 cm3. There was no significant difference in the volume and density of the anterior palate between different age groups and no significant difference in the volume between males and females (p value = 0.227). Conclusions: The anterior palate affords a considerable amount of bone volume which is similar or even more than other intraoral donor sites. The anterior palate is a potential donor site for bone harvesting and CBCT may be regarded as an ideal tool to analyze the amount of bone available for harvesting.

L’asthme équin est une maladie obstructive récurrente des voies respiratoires. De nombreux facteurs étiologiques ontété déterminés comme pouvant initier ou maintenir l’asthme équin sévère (AES), cependant l’exposition au foin restele facteur de risque principal. L’utilisation de traitements à base de corticoïdes sont efficaces en cas de crise maisinefficaces en l’absence de mesures sanitaires. Ainsi, depuis quelques années un dispositif permettant de « purifier »le foin à la vapeur a été développé, afin de diminuer la teneur en poussières et les antigènes microbiologiques présentsdans le foin. La physiopathologie de l’AES est complexe. Parmi les principaux acteurs de cette réponse immunitaire,les macrophages alvéolaires ont un rôle prédominant dans l’initiation et l’orientation de la réponse immunitaire. Ainsiétudier le rôle des macrophages des chevaux AES permettrait de mieux comprendre l’initiation de la réponseimmunitaire dans l’AES. Dans ce contexte, nous nous sommes interrogés sur l’influence du foin « à la vapeur » surla réponse immunitaire des chevaux AES lors d’un challenge in vivo et lors de la stimulation in vitro des macrophagesalvéolaires. Ainsi nous avons d’abord étudié la réponse systémique et locale des chevaux soumis à un challenged’exposition in vivo à du foin sec ou « à la vapeur ». La première partie de ce travail nous a permis d’observer uneffet bénéfique du foin « à la vapeur » sur le score de mucus trachéal des chevaux CTL et AES cependant nousn’avons pas observé un effet bénéfique significatif du foin « à la vapeur » sur la réponse cytologique et immunitaire.La deuxième partie du travail a permis d’étudier la réponse au foin « à la vapeur » à l’échelle des macrophagesalvéolaires. La microscopie en temps réel a mis en évidence des différences dans le comportement des macrophagesen réponse (1) à différents stimuli, (2) entre les chevaux AES et CTL, (3) entre les HDS provenant de foin sec ou defoin « à la vapeur ». La concentration en IL-1β était significativement plus élevée et la concentration en IL-10significativement plus faible chez les MA des chevaux AES comparés aux chevaux CTL. Une concentration en TNF-α plus élevée après stimulation in vitro a été observée chez les MA des chevaux AES et CTL. Cet état des lieux surla réponse des macrophages alvéolaires stimulés in vivo et in vitro pourra servir de base aux études futures nécessairespour conclure sur le rôle des MA dans le cas de l’AES. Cette triple approche à l’échelle du cheval, du poumon et dela cellule permet une vision globale de la réponse à un challenge d’exposition à du foin sec ou « à la vapeur » etpermet tout de même d’avoir un regard optimiste sur l’utilisation du foin « à la vapeur » pour les chevaux atteintsd’AES. / Equine asthma is a recurrent obstructive disease of respiratory tract. Several aetiologic factors are known to induceor maintain the severe equine asthma (sEA), however the hay exposure is the main risk factor. The use of treatmentswith corticoids are effective in case of crisis, but ineffective in the absence of sanitary measures. So, since severalyears a device allowing to purify the hay with steam was developed, in order to decrease the dust content and themicrobiological antigens within the hay. The pathophysiology of sEA is complex. Among the main actors of thisimmune response, the alveolar macrophages have an important role in the intiatiation and orientation of the immuneresponse. So, investigating the role of the equine alveolar macrophages of sEA horses would allow to betterunderstand the initiation of the immune response in the sEA. In this context, we focused on the influence of steamedhay on the immune response of sEA horses during an in vivo challenge and an in vitro stimulation of the alveolarmacrophages. First, we studied the systematic and local responses of horses submitted to an in vivo challengeexposure to dry and steamed hay. The first part of this work allowed us to show a beneficial effect of the steamedhay on the mucus tracheal score of sEA horses, however we did not observe any beneficial effect of the steamed hayon the cytological and immune response. The second part of the study allowed us to investigate the response of thealveolar macrophages to steamed hay. The real time microscopy showed differences in the behavior of macrophagesin response (1) to various stimuli, (2) between sEA and CTL horses (3) between HDS resulting from dry hay or fromsteamed hay. Moreover, the protein quantification of IL-1β was signifantly higher and the concentration of IL-10significantly lower in AM supernatant of sEA horses compared to CTL. The TNF-α concentration was higher on AMafter in vitro stimulation in sEA and CTL horses. These results on the alveolar macrophages reponse after both invivo challenge and in vitro stimulation, can be used as a basis for future studies in order to further characterize therole of AM in case of sEA. This triple approach on the horse, the lung and the cell scale allows a global vision of theresponse to an exposure challenge to dry or steamed hay and allows having an optimistic preliminary look on the useof the steamed hay for sEA horses.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22728号 / 医博第4646号 / 新制||医||1045(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 萩原 正敏, 教授 松田 道行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Magister Chirurgiae Dentium - MChD / This is a retrospective study of malignant tumours of the maxillofacial and oral region in children that presented over a 20 year period (1973 to 1993) at the Red Cross War Memorial Children's Hospital and Groote Schuur Hospital, Cape Town. Of the 352 children that were treated for a malignant tumour arising from various anatomic sites in the head and neck region, 30 were found to have had maxillofacial and oral involvement. This represented an incidence of 8,5%. Histologically, the majority of the tumours were non-odontogenic and mesenchymal in origin. The rhabdomyosarcoma was found to be the most common neoplasm, followed by the Burkitt's lymphoma. The age range was 6 months to 13.8 years (mean age 5.7 years). Males were more commonly affected than females, with a ratio of 1.3:1. There were 26 (86,7%) black patients and 4 (13,3%) white patients, representing a ratio of 6.5:1. Fifty percent of the cases were from the Eastern Cape. The mandible and the maxilla were the most common sites to be involved, followed by the soft tissues of the face. The most common presenting symptom was a painless swelling (73,3%) of the face. Twenty percent of the patients had "floating" or loose teeth. Radiographic features in the jaws were poorly circumscribed destructive lytic lesions with displacement of teeth. Histologic type was found to be the most significant variable affecting the outcome, with the Burkitt's lymphomas having the best prognosis and the rhabdomysarcomas the worst. The most common cause of death was metastases to the lungs. It is concluded that although malignant tumours of the maxillofacial and oral region in children are rare, their prognosis is poor. Therefore, any child presenting with a facial swelling should be viewed with suspicion.

Candida albicans is an increasingly important pulmonary fungal pathogen. Resident alveolar macrophages are important in host defense against opportunistic fungal infections. Activation of Group IVA cytosolic phospholipase A2α (cPLA2α) in macrophages initiates arachidonic acid (AA) release for production of eicosanoids, which regulate inflammation and immune responses. We investigated the ability of C. albicans to activate cPLA2α in unprimed alveolar macrophages and after priming with granulocyte macrophage colony-stimulating factor (GM-CSF), which regulates alveolar macrophage maturation. AA was released within minutes by GM-CSF-primed but not unprimed alveolar macrophages in response to C. albicans, and was blocked by soluble glucan phosphate (S-GP). The expression of the β-glucan receptor dectin-1 was increased in GM-CSF-primed macrophages, and AA release from GM-CSF-primed dectin-1-/- alveolar macrophages was reduced to basal levels. The enhanced activation of extracellular signal-regulated kinases and phosphorylation of cPLA2α on Ser-505 that occurred in GM-CSF-primed macrophages were reduced by MEK1 and Syk inhibitors, which also suppressed AA release. At later times after C. albicans infection (6 h), unprimed and GM-CSF-primed macrophages released similar levels of AA. The expression of cyclooxygenase 2 and prostanoid production at 6 hours was higher in GM-CSF-primed macrophages, but the responses were not dependent on dectin-1. However, dectin-1 contributed to the C. albicans-stimulated increase in TNF-α production that occurred in GM-CSF-primed macrophages. The results demonstrate that dectin-1 mediates the acute activation of cPLA 2α in GM-CSF-primed alveolar macrophages, but not in the more delayed phase of AA release and GM-CSF-dependent prostanoid production.

Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.

L’objectif principal de ce travail a été d’étudier le potentiel de mousses alvéolaires tridimensionnelles en carbure de silicium de forme béta (β-SiC) comme support de photocatalyseur, dans le but de mettre au point des réacteurs photocatalytiques structurés pour le traitement de l’air. Ces mousses alvéolaires de β-SiC de surface spécifique moyenne et de porosité très ouverte sont obtenues par la synthèse dite à mémoire de forme (Shape Memory Synthesis), consistant en la carburation contrôlée d’une mousse alvéolaire de polyuréthane préformée. Une étude de la dégradation de trois polluants sur des films minces en mode de lit léchant (la méthyléthylcétone, l’ammoniac et le sulfure d’hydrogène) a tout d’abord permis de sélectionner trois photocatalyseurs d’intérêt parmi six références commerciales avant d’être immobilisés sur les mousses de β-SiC. Après une étape d’optimisation en termes de taille d’alvéoles, de nature et quantité de photocatalyseur, le média photocatalytique TiO2/mousses de β-SiC a été caractérisé et ses performances comparées en mode mono-passage ainsi qu’en mode de recirculation du flux dans une enceinte de 2 m3, à celles d’un film mince de TiO2 et d’un média photocatalytique commercial de référence. Le média photocatalytique TiO2/mousses de β-SiC présente des performances nettement améliorées par rapport à celles du média référent. Les mousses jouent un rôle de mélangeur statique et permettent une meilleure utilisation du volume du réacteur, en augmentation la densité de photocatalyseur par unité de volume tout en maintenant une illumination du cœur du réacteur acceptable ainsi que des pertes de charge très limitées. / The main objective of this work was to study the potential of three-dimension beta silicon carbide (β-SiC) alveolar foams for use as photocatalyst support, targeting the implementation of structured photocatalytic reactors for air treatment. Medium surface area β-SiC alveolar foams were synthesized according to the Shape Memory Synthesis concept, consisting in the controlled carburization of a preshaped polyurethane foam. First, the degradation of three model pollutants (methylethylketone, ammonia and hydrogen sulfide) was performed over TiO2 thin layers in a flow-through reactor for selecting three photocatalysts of interest – Hombikat UV100, PC500 and P25 TiO2 – among six commercial standards. The powderly photocatalysts were further immobilized onto β-SiC foams. After an optimization step in terms of mean cell size, light transmission, photocatalyst nature and weight content as well as of the immobilization method, the TiO2/β-SiC foam photocatalytic media was characterized and its photocatalytic behaviour was compared in a single-pass mode as well as in a recirulation mode inside a 2 m3 chamber, to those obtained on a TiO2 thin layer and with a well-known commercial photocatalytic felt media made from quartz fibers supporting sol-gel TiO2. The photocatalytic media elaborated with β-SiC alveolar foams exhibited superior performances compared to that of the commercial felt standard. The foams acted as static mixing within the reactor and allowed a more efficient use of the reactor volume, by increasing the photocatalyst density per reactor volume unit, while maintaining however a suitable illumination within the reactor core as well as very low pressure drops.