<p>Teleosts take up metals by two major pathways: gills and/or gut. Past research is heavily focused on branchial uptake despite evidence that the gastro-intestinal tract (GIT) is the dominant route in some natural environments. To address this information gap, my thesis characterizes uptake mechanisms of Cd and Ca along the GIT of <em>Oncorhynchus mykiss</em>. Toxic effects of Cd, protective effects of Ca against Cd uptake, and Cd distribution within fish after ingestion are also explored.</p> <p>Four-week dietary Cd exposure affected growth and Ca regulation, while causing toxicity at the subcellular level. Elevated Ca in diets protected against accumulation and altered subcellular handling of Cd. Pre-exposure to different diets changed unidirectional uptake and binding rates of Cd and Ca, although they remained highly correlated. Binding rates of Cd to mucus can predict absorption rates of Cd<strong>.</strong></p> <p>A variety of <em>in vitro </em>and <em>in vivo </em>experiments on four distinct GIT segments (stomach, anterior-, mid-, and posterior- intestine) were undertaken to determine specific mechanisms of Cd and Ca uptake in freshwater trout. Cd transport was unaffected by solvent drag, but was stretch- and temperature- sensitive. Strong evidence for a common pathway for Ca and Cd transport was obtained. Cd also appeared to be taken up in part by zinc (ZIP-like) transporters and the divalent metal transporter DMT1. Ca uptake along the GIT appeared to be carrier-mediated, time- and concentration- dependent, but was not affected by solvent drag, or by Na concentration. Mucosal Cd did not inhibit Ca uptake. Ca, but not Cd, uptake rates were much lower in sea water-acclimated trout. Seawater and freshwater fish accumulated similar whole body Cd concentrations when fed contaminated diets for three weeks, but the majority of Cd in seawater trout remained in the posterior intestine tissue, while freshwater trout had higher internal burdens.</p> <p>This thesis advances the knowledge of metal uptake along the GIT of trout.</p> / Doctor of Science (PhD)

To assess the technical success rate, and evaluate the clinical outcome, length of hospital stay, and cost of palliative gastro-duodenal stenting in a single-centre. Materials and methods Eight-seven patients referred for insertion of a gastroduodenal stent between April 1999 and April 2004 were recruited to a non-randomized, before and after intervention study performed in a single centre. Demographic data, diagnosis and symptoms along with clinical and technical outcomes were recorded. Results The technical success rate was 84/87 (96.6%), with inability to traverse the stricture in three patients. No immediate complications were demonstrated. There was marked improvement after stent placement with resolution of symptoms and commencement of dietary intake in 76 patients (87%). Stenting resulted in improved quality of life as reflected by an increase in Karnofsky score from 44/100, to 63/100 post-procedure. Late complications included perforation (n=1), migration (n=1) and stent occlusions due to tumour ingrowth/overgrowth (n=7; mean 165 days). Mean survival was 107 days (range 0¿411 days). Median hospital stay post-stent placement was 5.5 days, (range 1¿55 days) with a majority of patients (75%) discharged home. The mean cost of each treatment episode was £4146 ($7132 $US, ¿6,028 EUROS). Conclusion The present series confirms that combined endoscopic and radiological gastroduodenal stenting is a highly favourable treatment for patients with inoperable malignant gastric outlet obstruction. The results suggest that this minimally invasive procedure has a very high technical success rate, whilst at the same time providing excellent palliation of symptoms with improved quality of life in the majority of patients.

Le charbon activé est l'agent le plus fréquemment recommandé pour la décontamination gastro-intestinale des enfants empoisonnés en Amérique du Nord. Pourtant, ses risques et bénéfices dans la population pédiatrique sont insuffisamment documentés dans les écrits scientifiques, et son efficacité est incertaine. À défaut de données probantes, nous avons réalisé trois études pour évaluer l'usage du charbon activé dans une population pédiatrique empoisonnée. 1. La première étude visait à valider l'utilisation du *Poisoning Severity Score* pour évaluer la gravité de l'intoxication et la progression de la toxicité dans une population pédiatrique empoisonnée par une substance carbo-adsorbable ; 2. La seconde étude avait pour objectifs de décrire la fréquence d'utilisation du charbon activé, d'évaluer les déterminants potentiels de son administration, et d'estimer l'association entre la décontamination par charbon activé et les issues cliniques des enfants empoisonnés par une substance carbo-adsorbable, telles que la progression de la toxicité ; 3. La troisième étude visait à synthétiser les connaissances sur l'effets des additifs de goût pour améliorer la palatabilité du charbon activé. Les deux premières études rétrospectives multicentriques utilisaient des données de patients pédiatriques ayant consulté à l'urgence de trois centres hospitaliers du Québec entre 2013 et 2016 dans les douze heures suivant l'ingestion d'une dose potentiellement toxique d'une substance carbo-adsorbable. La première étude observationnelle rétrospective menée chez les 0 à 17 ans a permis de valider l'utilisation du *Poisoning Severity Score* à des fins de recherche en toxicologie clinique, avec une bonne fiabilité inter-évaluateurs. Des modèles de régression logistique ont permis d'étudier sa capacité discriminante et sa calibration. La comparaison de la performance du *Poisoning Severity Score* à celle du *Pediatric Logistic Organ Dysfunction Score* (PELODS) suggère que le PSS est plus adapté que le PELODS pour caractériser la gravité de l'intoxication et la progression de la toxicité dans notre population d'étude. La seconde étude de cohorte rétrospective multicentrique, effectuée chez les 0-5 ans, nous a permis de mesurer que le charbon activé a été utilisé pour décontaminer 24% (IC 95% 19 à 29%) des enfants empoisonnés par une substance carbo-adsorbable au Québec. Majoritairement, ces enfants se sont présentés à l'urgence en étant pas ou peu symptomatiques. La plupart d'entre eux n'ont pas expérimenté de progression de la toxicité majeure, comme le reflètent les mesures du *Poisoning Severity Score*. Dans les trois centres hospitaliers québécois où notre population d'étude a consulté, un délai post-ingestion court (< 90 minutes) était l'indication privilégiée pour l'administration du charbon. La présence de comorbidités et d'un score PELODS intermédiaire ou élevé étaient également associés à une probabilité plus grande de décontamination par charbon activé. Les enfants traités par charbon présentaient une diminution de 30% du risque d'augmentation de la toxicité durant les 12 premières heures, mais une probabilité deux fois plus élevée d'être admis à l'hôpital ou aux soins intensifs, et d'avoir une durée de séjour de 12 heures et plus. Cependant, ces différences avec les enfants non décontaminés n'étaient pas statistiquement significatives dans notre cohorte, rendant les résultats de cette comparaison non concluants. Finalement, notre troisième étude était une revue systématique de la littérature, qui nous a permis d'observer que peu d'études de bonne qualité méthodologique ont été consacrées à l'effet des additifs de goût sur la palatabilité du charbon. Cette pratique est pourtant largement répandue dans les milieux de soins pour optimiser la décontamination gastrointestinale par charbon activé. L'utilisation d'additifs de goût tels que le cola ou le chocolat pourrait être une solution facilement accessible pour optimiser la décontamination par charbon activé chez les enfants empoisonnés, mais les connaissances actuelles sont insuffisantes pour soutenir cette pratique. En conclusion, cette thèse a permis de collecter des informations sur les pratiques d'utilisation du charbon activé dans une population pédiatrique empoisonnée par une substance carbo-adsorbable. Nos résultats contribueront à l'élaboration du protocole d'un essai clinique randomisé multicentrique pancanadien visant à évaluer l'efficacité du charbon activé dans cette population. / Activated charcoal is the most frequently recommended agent for gastrointestinal decontamination of poisoned children in North America. However, itsrisks and benefits in the pediatric population are insufficiently documented in the scientific literature, and its effectiveness is uncertain. In the absence of evidence, we conducted three studies to evaluate the use of activated charcoal in a pediatric poisoned population. 1. The first study aimed to validate the use of the Poisoning Severity Score to assess the severity of intoxication and the toxicity progression in a pediatric population poisoned by a carbo-adsorbable substance; 2. The objectives of the second study were to describe the frequency of use of activated charcoal, to assess potential determinants of its administration, and to estimate the association between activated charcoal decontamination and clinical outcomes of children poisoned by a carbo-adsorbable substance, such as the toxicity progression; 3. The third study aimed to synthesize knowledge on the effects of taste additives to improve the palatability of activated charcoal. The first two retrospective multicenter studies used data from pediatric patients who visited the Emergency Department of three Québec hospital centers between 2013 and 2016 within twelve hours after ingesting a potentially toxic dose of a carbo-adsorbable substance. The first retrospective observational study conducted in children aged 0- to 17-years validated the use of the Poisoning Severity Score for clinical toxicology research purposes, with good inter-rater reliability. Logistic regression models were used to study its discrimination and calibration. Comparison of the performances of the Poisoning Severity Score with that of the Pediatric Logistic Organ Dysfunction Score (PELODS) showed that the PSS is better suited than the PELODSto predict the severity of intoxication and the toxicity progression in our study population. The second retrospective multicenter cohort study, conducted in children aged 0 to 5 years, allowed us to measure that activated charcoal was used to decontaminate24% (95% CI 19 to 29%) of children poisoned by a carbo-adsorbable substance in Québec. Most of these children presented to the Emergency Department with little or no symptoms. They did not experience a significant toxicity progression, as reflected by the Poisoning Severity Score measures. In the three Québec hospital centers where our study population consulted, a short post-ingestion time (<90 minutes) was the preferred indication for activated charcoal administration. The presence of comorbidities and an intermediate or high PELODS were also associated with a greater likelihood of decontamination with activated charcoal. Charcoal-treated children had a 30% lower risk of increased toxicityin the first 12 hours, but twice the likelihood of being admitted to the hospital or intensive care unit, and of having a length of stay of 12 hours or more. However, these differences with non-decontaminated children were not statistically significant in our cohort, making the results of this comparison inconclusive. Finally, our third study was a systematic review of the literature, which allowed us to observe that few studies of good methodological quality have addressed the effect of taste additives on activated charcoal’s palatability. However, this practice is widely used to optimize gastrointestinal decontamination with oral activated charcoal in clinical care. The use of taste additives such as cola or chocolate could be a readily available solution to optimize activated charcoal decontamination in poisoned children. Still, current knowledge is insufficient to support this practice.In conclusion, this thesis has collected information on the use of activated charcoal in a pediatric population poisoned by a carbo-adsorbable substance. Our results will contribute to developing a protocol for a pan-Canadian multicenter randomized controlled trial to evaluate the efficacy of activated charcoal in this population.

Streptococcus thermophilus est la bactérie lactique la plus utilisée après Lactococcus lactis dans l'industrie laitière pour la fabrication de yaourts et de fromages à pâte cuite (Emmental, gruyère), filée (Mozarella) ou pressée (Cheddar). Il s'agit du seul streptocoque à avoir le statut de bactérie GRAS (Generally Recognized As Safe). Dans un premier temps le potentiel probiotique de 30 souches de S. thermophilus de différentes origines a été testé par l'étude de leurs capacités à résister aux différentes conditions de stress rencontrées pendant leur passage dans le tractus gastro-intestinal (bas pH, sels biliaires et stress oxydant), de leur capacité à adhérer aux cellules épithéliales intestinales et de leurs propriétés immunomodulatrices. La majorité des souches réduit la production d'interleukine IL-8 (pro-inflammatoire) alors qu'elles induisent la production d'interleukine IL-10 (anti-inflammatoire) et l'IL-12 (pro-inflammatoire). Sur la base du rapport IL-10/IL-12, qui permet d'apprécier le potentiel anti-inflammatoire d'une souche, nous avons observé que certaines d'entre-elles pourraient avoir un fort potentiel anti-inflammatoire. L'Analyse en Composantes Principales (ACP) nous a permis de séparer les souches en 6 catégories différentes présentant des propriétés distinctes. A l'intérieur de chaque classe, une variabilité entre les souches a été observée et des caractéristiques intéressantes identifiées. Cependant, aucune des classes ne peut être considérée comme contenant le probiotique « parfait ». Suite à cette étude et sur la base de sa résistance aux stress gastriques et de ses capacités d'adhésion, et sachant que la séquence de son génome est disponible, la souche LMD-9 a été sélectionnée pour la deuxième partie de ce travail, à savoir la construction d'un outil basé sur la technologie R-IVET pour étudier l'état physiologique de S. thermophilus dans le tractus digestif. L'outil R-IVET mis au point se compose de deux éléments: un vecteur plasmidique portant le gène cre codant une recombinase spécifique dépourvu de son promoteur et une cassette chromosomique composée d'un gène de résistance à la spectinomycine flanqué par des sites loxP, reconnus par la recombinase Cre. La fonctionnalité de l'outil R-IVET a ensuite été testée par le clonage de trois promoteurs différents de S. thermophilus (PprtS, Pshsp and Plac) en amont de cre. Le système a été valide in vitro avec les trois promoteurs et in vivo avec le promoteur Plac / Streptococcus thermophilus is a lactic acid bacterium used after Lactococcus lactis in the dairy industry for the production of yogurt and cheeses like Emmental, Gruyere, Mozarella and Cheddar. It is the only streptococcus to have the GRAS (Generally Recognized As Safe) status. In this work, the probiotic potential of 30 S. thermophilus strains from different origins was tested by studying their ability to resist different stress conditions encountered during their passage through the GIT (low pH, bile salts and oxidative stress), their ability to adhere to intestinal epithelial cells and their immunomodulatory properties. Majority of the strains reduced the production of interleukin IL-8 (pro-inflammatory) and induced the production of interleukin IL-10 (anti-inflammatory) and IL-12 (pro-inflammatory). On the basis of the ratio IL-10/IL-12 which allows to evaluate the anti-inflammatory potential of a probiotic, several strains appeared to have a high the anti-inflammatory potential. Principal Component Analysis (PCA) allowed us to classify strains in 6 different categories with different properties. Within each class, variability and interesting features were observed, but none of the classes could be considered as containing the perfect probiotic. Following this study and on the basis of its resistance to gastric stress and its adhesion capacity and knowing that its genome sequence is available, the strain LMD-9 was selected for the second part of this work, namely the construction of a tool based on R-IVET to study the physiological state of S. thermophilus in the digestive tract. This tool is composed of two elements: a plasmid vector (pULNcreB), carrying the gene cre encoding a site-specific recombinase without its promoter and a chromosomal cassette composed of a gene of resistance to spectinomycin flanked by loxP sites which are recognized by the recombinase Cre. The functionality of the tool R-IVET was then tested by cloning three different promoters of S. thermophilus (PprtS, Pshsp and Plac) upstream of cre. System was valid in vitro with all the three promoters and in vivo by using the lactose operon promoter Plac

A Síndrome da Imunodeficiência Adquirida (AIDS) é uma doença de amplo espectro de manifestações, sendo razão de preocupação para qualquer autoridade sanitária. A terapêutica da AIDS é complexa sendo utilizados vários medicamentos, diversas vezes ao dia. Deste modo, objetivou-se o desenvolvimento de formas farmacêuticas sólidas como comprimidos tamponados mastigáveis (CTM), comprimidos com revestimento gastro-resistentes (CRGR) e pellets (PEL) para a veiculação de didanosina (ddl). Seis especialidades farmacêuticas na forma de CTM foram estudadas quanto ao perfil de dissolução, pH do meio e capacidade neutralizante ácida (CNA). Formulações teste de CTM foram propostas visando obter CNAs e perfis de dissolução adequados. Também foram testadas formulações de comprimidos e de pellets para posterior revestimento com filme gastro-resistente derivado do ácido metacrílico. Os ensaios de dissolução das amostras de CTM revelaram diferenças nas características de liberação do fármaco. Também foram observadas diferenças relacionadas a CNA. As formulações de CTM propostas apresentaram, na maioria dos casos, adequados perfis de dissolução e CNA. As formulações CRGR que receberam revestimento gastro-resistente apresentaram perfis de dissolução de ddl adequados, entretanto os comprimidos testados intumesceram em meio ácido, indicando descontinuidade do filme polimérico sobre os comprimidos. Testes para a produção de pellets veiculando ddl mostraram-se adequados quanto à morfologia e dissolução do fármaco, o mesmo sendo observado após o revestimento com filme gastro-resistente. / The Acquired Immune Deficiency Syndrome (AIDS) is a disease that manifests itself in a myriad of ways. Because of this, the condition has been subject of concern to all sanitary authorities. The treatment of AIDS is complex and many types of medicine are used, many times a day. The objective of the present study was to develop solid pharmaceutical dosage forms such as buffered chewable tablets (CTM), gastro-resistant coating tablets (CRGR) and pellets (PEL) for the loading of didanosine (ddl). Six pharmaceutical specialties in the form of CTM were studied so as to identify the profile of the dissolution, the pH of the environment, and the neutralizing acid capacity (CNA). The use of CTM tests formulations was proposed with the objective of obtaining adequate CNA and dissolution profiles. Different compositions of tablets and pellets were tested for a later addition of gastro-resistant film derived from the methacrylic acid. The experiments on the dissolution of the sample of CTM showed differences in the characteristic of the release of the substance. Differences related to the CNA were also observed. The formulations of the CTM proposed showed to have, in the most number of the cases, both adequate dissolution behavior and CNA. The formulations of the CRGR that had received the gastro-resistant coating showed adequate profile of ddl dissolution; the tested tablets, however, swelled in the acid environment, therefore indicating a lack of continuity of the polymeric film over the tablets. The tests for the production of pellets showed adequate results as to its morphology and dissolution of ddl. The same was observed after coating the pellets with gastro-resistant film.

Lorsqu’il est surexprimé ou activé constitutivement par mutation, le récepteur tyrosine kinase KIT est impliqué dans le développement de pathologies prolifératives comme les mastocytoses, les tumeurs stromales gastro-intestinales (GIST) et certaines leucémies. La voie de signalisation KIT représente donc une cible thérapeutique majeure en oncologie. Le développement d’une nouvelle classe de molécules pharmacologiques appelées inhibiteurs de tyrosine kinase (ITK) est en plein essor. Un exemple majeur d’ITK est l’imatinib qui cible, entre autre, KIT et est efficace dans la plupart des GIST. Cependant, le traitement aux ITK est souvent confronté au phénomène de résistance primaire ou acquise par mutation secondaire. C’est pourquoi nous cherchons à développer de nouveaux composés ciblant KIT ou les voies de transductions activées par ses formes oncogéniques, et ce par 3 approches.Nous avons récemment montré que les mutants oncogéniques de KIT ont une localisation intracellulaire alors que KIT sauvage est exprimé à la membrane. L’inhibition de l’activité kinase des mutants restaure une localisation normale. A partir de cette observation, nous avons créé et validé un test de criblage par cytométrie mesurant la relocalisation de KIT muté à la surface cellulaire. Le criblage d’une chimiothèque nous a permis de sélectionner de nouveaux inhibiteurs de la signalisation KIT actifs sur des lignées cellulaires mutées pour KIT.Nous avons utilisé la technique du phage display pour sélectionner des anticorps au format scFv et VHH spécifiques de la partie intracellulaire de KIT mutant. Lors de leur expression dans le cytosol (on parle alors d’intrabodies), leur fixation au niveau de KIT inhibe soit directement l’activité kinase, soit le recrutement de partenaires de signalisation. Nous avons obtenu des intrabodies de différentes spécificités vis-à-vis des formes de KIT dont la caractérisation fonctionnelle est en cours Les intrabodies inhibiteurs seront utilisés pour cribler des chimiothèques par ELISA. Les molécules chimiques recherchées empêcheront la fixation des intrabodies sur la région intracellulaire de KIT. On sélectionnera donc des molécules inhibant potentiellement l’oncogénicité de KIT.Nous avons développé des anticorps au format scFv-Fc par phage display qui reconnaissent le domaine extracellulaire de KIT. Deux des anticorps sélectionnés inhibent donc la signalisation induite par le SCF. Dans des lignées de leucémie exprimant KIT WT, nous avons montré que l’utilisation de ces anticorps entraîne une diminution de la viabilité cellulaire. De plus, ils diminuent également la prolifération de lignées de leucémie à mastocytes sensibles et résistantes à l’imatinib (HMC11 et HMC12, respectivement). Ils représentent donc des outils thérapeutiques potentiels pour le traitement des pathologies impliquant KIT ainsi que pour contourner la résistance aux ITK de certains mutants. / When overexpressed or constitutively active by mutation, the tyrosine kinase receptor KIT is involved in some proliferative diseases such as gastro-intestinal stromal tumors (GIST), mastocytosis and some leukemia. Therefore, KIT signaling represents a major target in oncology. Development of a new therapeutic class called tyrosine kinase inhibitors is in full expansion. A major example of TKI is imatinib which targets KIT and is efficient in the majority of GIST cases. However, TKI treatment is often unpaired by primary or acquired resistance due to secondary mutations. That is why we aim to develop new compounds to target KIT or associated signaling pathways by three strategies.We have recently shown that oncogenic KIT mutants are intracellularely localized whereas WT KIT is expressed at the cell surface. Kinase activity inhibition leads to membrane mutants’ relocalization. Based on this finding, we developed and validated a screening assay measuring mutants’ relocalization by cytometry. Chemicals library screening allows us to select new KIT signaling inhibitors active on KIT mutant cell lines.We used phage display to generate scFv and VHH antibodies which are specific to KIT intracellular domain. When expressed in cytoplasm (they are called intrabodies), their binding on KIT inhibits kinase activity directly or signaling partners’ recruitment. Selected intrabodies are specific to various KIT isoforms and their functional characterization is ongoing. KIT inhibitory intrabodies will be used to screen chemical libraries by ELISA for drugs that block intrabodies binding on KIT intracellular domain. We will then select molecules that potentially inhibit KIT oncogenicity.We developed scFv-Fc antibodies by phage display that recognize KIT extracellular domain. Two selected antibodies inhibit SCF induced signaling. In WT KIT expressing leukemic cell lines, we showed that antibody treatment reduces cell viability. Moreover, they also diminish cell proliferation of 2 imatinib sensitive and resistant mast cell leukemia cell lines (HMC1.1 and HMC1.2, respectively). They represent potential therapeutic tools for treatment of KIT involved diseases and for bypass TKI resistance of some mutants.

A Síndrome da Imunodeficiência Adquirida (AIDS) é uma doença de amplo espectro de manifestações, sendo razão de preocupação para qualquer autoridade sanitária. A terapêutica da AIDS é complexa sendo utilizados vários medicamentos, diversas vezes ao dia. Deste modo, objetivou-se o desenvolvimento de formas farmacêuticas sólidas como comprimidos tamponados mastigáveis (CTM), comprimidos com revestimento gastro-resistentes (CRGR) e pellets (PEL) para a veiculação de didanosina (ddl). Seis especialidades farmacêuticas na forma de CTM foram estudadas quanto ao perfil de dissolução, pH do meio e capacidade neutralizante ácida (CNA). Formulações teste de CTM foram propostas visando obter CNAs e perfis de dissolução adequados. Também foram testadas formulações de comprimidos e de pellets para posterior revestimento com filme gastro-resistente derivado do ácido metacrílico. Os ensaios de dissolução das amostras de CTM revelaram diferenças nas características de liberação do fármaco. Também foram observadas diferenças relacionadas a CNA. As formulações de CTM propostas apresentaram, na maioria dos casos, adequados perfis de dissolução e CNA. As formulações CRGR que receberam revestimento gastro-resistente apresentaram perfis de dissolução de ddl adequados, entretanto os comprimidos testados intumesceram em meio ácido, indicando descontinuidade do filme polimérico sobre os comprimidos. Testes para a produção de pellets veiculando ddl mostraram-se adequados quanto à morfologia e dissolução do fármaco, o mesmo sendo observado após o revestimento com filme gastro-resistente. / The Acquired Immune Deficiency Syndrome (AIDS) is a disease that manifests itself in a myriad of ways. Because of this, the condition has been subject of concern to all sanitary authorities. The treatment of AIDS is complex and many types of medicine are used, many times a day. The objective of the present study was to develop solid pharmaceutical dosage forms such as buffered chewable tablets (CTM), gastro-resistant coating tablets (CRGR) and pellets (PEL) for the loading of didanosine (ddl). Six pharmaceutical specialties in the form of CTM were studied so as to identify the profile of the dissolution, the pH of the environment, and the neutralizing acid capacity (CNA). The use of CTM tests formulations was proposed with the objective of obtaining adequate CNA and dissolution profiles. Different compositions of tablets and pellets were tested for a later addition of gastro-resistant film derived from the methacrylic acid. The experiments on the dissolution of the sample of CTM showed differences in the characteristic of the release of the substance. Differences related to the CNA were also observed. The formulations of the CTM proposed showed to have, in the most number of the cases, both adequate dissolution behavior and CNA. The formulations of the CRGR that had received the gastro-resistant coating showed adequate profile of ddl dissolution; the tested tablets, however, swelled in the acid environment, therefore indicating a lack of continuity of the polymeric film over the tablets. The tests for the production of pellets showed adequate results as to its morphology and dissolution of ddl. The same was observed after coating the pellets with gastro-resistant film.

Gastronomy belongs among the important elements of the French national identity and at the same time it is one of the main tourist attractions. Which place and why does the gastronomy have among the modern trends of public diplomacy and how is the French gastro-diplomacy formed on the online social media? There are certain long-lasting tensions visible in the French gastronomic discourse, for example between the Republican idea of unity and the foreign policy strategy of supporting diversity. However, historical research shows that these aspects are not excluding one another, they are more like two sides of the same coin. Gastro-diplomacy is then understood as a narrow dimension of the foreign policy, namely as a part of public cultural diplomacy. In the framework of contemporary French gastro-diplomacy, it is possible to observe the employment of modern instruments, such as the communication through online social networks. Combined with the bet on the long-standing good image of French cuisine, it is one of the ways in which France prove successful in the international arena. It is also a sign of strategic behaviour against the standardization of food products. Quantitative and qualitative analysis of Facebook, Twitter and Instagram posts showed that during the period 1. 1. 2009 - 30. 6. 2017,...

Il y a actuellement une pression mondiale pour revoir les pratiques d'utilisation des antimicrobiens (UAM) en production animale afin de limiter la propagation de bactéries résistantes aux antibiotiques. Conséquemment, les Producteurs de Poulet du Canada examinent la possibilité de réduire leur UAM en supprimant les antibiotiques médicalement importants en médecine humaine (AIM) des programmes préventifs avec la mise en place de leur stratégie de réduction de l’UAM. Cependant, les informations sont rares sur les conséquences de telles approches dans un contexte canadien. L'objectif de cette thèse était d'étudier les impacts sur les performances zootechniques, le contrôle des maladies intestinales et le microbiote cécal de deux stratégies de réduction de l'UAM dans des troupeaux commerciaux de poulets de chair par rapport à une UAM conventionnelle. Sur sept fermes commerciales de poulets de chair, un poulailler a été attribué aux traitements de réduction des antibiotiques pour six troupeaux consécutifs, tandis qu'un poulailler similaire sur le même site a été alloué à l'UAM conventionnelle (CONV) pour six troupeaux consécutifs (n = 84). Les stratégies de réduction des antibiotiques consistaient en l'utilisation continue d'ionophores dans l'alimentation sans (TX1) ou avec de l'acide butyrique (TX2). Aucune différence statistique (p > 0.05) n’a été notée entre TX1, TX2 et CONV sur les performances zootechniques et la santé intestinale. Les comptes d’oocystes d’Eimeria spp. étaient significativement (p < 0.05) inférieurs entre 22 et 34 jours d'âge dans les troupeaux CONV comparé aux TX1 et TX2. Le type de programme antibiotique a eu un impact relativement mineur (valeur R = 0.039), mais statistiquement significatif (p = 0.002), sur le microbiote cécal, tandis que les facteurs environnementaux ont montré les corrélations significatives (p = 0.001) les plus fortes avec le microbiote. Parmi les composantes du microbiote cécal associées à la croissance, le gain quotidien moyen (GMQ) était significativement associé à la Richesse bactérienne (p < 0.05). L’abondance relative de la famille bactérienne Lachnospiraceae fut la mesure la plus fortement corrélée à un GMQ augmenté, tandis que l’abondance relative de nombreuses familles bactériennes, incluant les Porphyromonadaceae, les Planococcaceae et les Veillonellaceae, fut corrélée à un faible GMQ. Ces taxons défavorables formaient un vaste réseau de corrélations positives entre elles, et négativement corrélées aux Lachnospiraceae. En conclusion, ces travaux ont contribué à améliorer la résilience de l'industrie avicole en fournissant des stratégies alternatives aux AIM pour prévenir les maladies intestinales. Des connaissances importantes sur le microbiote cécal des poulets de chair furent générées et pourront considérablement influencer les directions futures de la manipulation du microbiote pour favoriser la croissance. Par exemple, un paradigme important a été remis en question en illustrant que les additifs médicamenteux dans l'alimentation n’influencent que marginalement le microbiote cécal et que ce sont plutôt des facteurs environnementaux qui sont fortement impliqués dans la formation des communautés bactériennes cécales. La clé pour développer un microbiote cécal idéal chez les poulets de chair pourrait résider dans la capacité d'influencer ces facteurs, plus particulièrement l'exposition précoce à des communautés bactériennes bénéfiques et le contrôle de la flore résidente spécifique à la ferme. / There is a global pressure to review current antimicrobial use (AMU) practices in animal production and limit large-scale propagation of antibiotic resistant microorganisms. Consequently, the Chicken Farmers of Canada are examining the possibility to responsibly reduce AMU by discontinuing medically important antibiotics (MIAs) for humans from disease prevention programs of broiler chicken flocks through the implementation of their Antimicrobial Use Reduction Strategy. However, information is sparse on the consequences of such approaches in a Canadian commercial poultry production context. The general objective of this thesis was to investigate the impacts of two strategies reducing AMU in commercial broiler chicken flocks on zootechnical performance, control of intestinal diseases and the cecal microbiota compared to conventional AMU. On seven commercial broiler chicken farms, a house was allocated to the antibiotic reduction treatments for six consecutive flocks, while a similar house on the same premises was assigned to the conventional AMU (CONV) for six consecutive flocks (n = 84). The antibiotic reduction strategies consisted of continuous in-feed ionophores without (TX1) or with butyric acid (TX2). There were no statistical differences (p > 0.05) between TX1, TX2 and CONV for zootechnical performance and intestinal health. Predicted Eimeria spp. oocysts were significantly lower (p < 0.05) between 22 to 34 days of age in CONV flocks compared to TX1 and TX2. The type of antibiotic program had a relatively minor impact (R-value = 0.039), but statistically significant (p = 0.002), on the cecal microbiota composition, while environmental factors such as the farm and flock cycle showed the strongest statistically significant (p = 0.001) correlations with the microbiota composition (R-values of 0.239 and 0.374, respectively). Amongst the cecal microbiota components associated with weight gain, the average daily gain (ADG) was significantly associated with bacterial Richness (p < 0.05). The relative abundance of the bacterial family Lachnospiraceae was the most important measure correlated with ADG, while the relative abundance of numerous bacterial families, including Porphyromonadaceae, Planococcaceae and Veillonellaceae, were correlated with decreased growth rate. These unfavourable taxa formed a large network of positive correlations, indicating potential co-occurring synergies between these undesirable taxa. This network was also negatively correlated to Lachnospiraceae. In conclusion, the findings in this work contributed to improve the sustainability of the modern poultry industry by providing feasible alternatives to the practice of using MIAs for the prevention of intestinal diseases in broiler chickens. This project also generated important knowledge on the cecal microbiota of broiler chickens that could considerably influence future directions of microbiota manipulation in a perspective of improving zootechnical performance. For instance, an important paradigm was challenged by the indication that in-feed antibiotics and prebiotics may only influence marginally the microbiota during grow-out. Rather, this work suggests environmental factors are strongly involved in shaping the bacterial communities residing in the ceca of broiler chickens. Hence, the key to successfully develop an ideal cecal microbiota in broiler chickens may reside in the ability to influence such factors, more specifically the early exposure to beneficial bacterial communities and the control of farm-specific resident flora.

O refluxo gastro-esofágico é considerado fator responsável pela dificuldade alimentar na infância. A ocorrência de experiências negativas como vômitos, regurgitações, muitas vezes associadas a engasgos, esofagite, disfagia, odinofagia, pirose e dor retroesternal geram comportamentos de aversão ou recusa alimentar e desorganizam o processo de deglutição e alimentação. O presente estudo teve por objetivo avaliar a deglutição em crianças com diagnóstico clínico de refluxo gastroesofágico (RGE). Foram selecionadas 37 crianças, com diagnóstico clínico de refluxo gastro-esofágico e refluxo gastro-esofágico associado a queixas de dificuldades alimentares, com idades variando de 7 meses a 3 anos e 1 mês, idade média de 15,35 meses, sendo 25 (67,6%) do gênero masculino e 12 (32,4%) do gênero feminino. Participaram do grupo controle 15 crianças, saudáveis (estado geral e nutricional), que foram cuidadosamente triadas para assegurar adequado desenvolvimento neuropsicomotor e ausência de sintomas de refluxo gastro-esofágico e problemas respiratórios de repetição, na faixa etária de 6 meses a 3 anos e 2 meses, idade média de 20,5 meses; 9 (60,0%) do gênero feminino e 6 (40,0%) do gênero masculino. Para a avaliação funcional da deglutição foram utilizadas dietas de consistências líquida, pastosa e sólida em volume inicialmente de 5 ml e após em volume livre, habitualmente utilizado pela criança. Na avaliação videofluoroscópica, utilizou-se das dietas de consistências líquida e pastosa, em volume livre para o leite e 5 ml para a dieta pastosa, adicionadas ao contraste de bário. As crianças com refluxo gastro-esofágico apresentaram alterações na avaliação clínica com ingestão menos freqüente de consistência sólida, presença de náusea, recusa alimentar, engasgos e irritabilidade alimentar. Na avaliação objetiva para o alimento de consistência líquida houve penetração laríngea e movimento compensatório de cabeça em extensão, sendo este último também observado para o alimento de consistência pastosa. Entretanto, não houve diferença entre os tempos das fases da deglutição. O estudo permitiu concluir que crianças com RGE apresentam dificuldades relacionadas à aceitação alimentar, porém os tempos da dinâmica orofaríngea da deglutição não se alteram. / Gastroesophageal reflux is considered cause of infants feeding disorder. Negative experience such as vomiting, regurgitation; several times may be associated to choking, dysphagia and painfull swallowing produce aversion or feed refusal and causes a break up in the swallowing and feeding processes. This study evaluated the swallowing process in children with gastroesophageal reflux (GER), confirmed clinically and radiographically. We selected 37 children, with GER and GER complaints of feeding disorders, ages range from 7 months to 37 months, mean age of 15,4 months, consisted 25 males (67,6%) and 12 females (32,4%). The control group (GC) consisted of 15 healthy children (general and nourishing states), carefully chosen for not having any symptoms of GER, repetitive breathing disorders or developmental delays. The ages varied form 6 to 38 months, with mean age of 20,5 months, being 6 males (40%) and 9 females (60%). Swallowing evaluation (functional) considered three diets consistency: liquid, semi-solid and solid, beginning with 5 ml followed by free volume taken habitually by children. Free volume of milk and 5 ml of semi-solid, mixed with barium, were used during the videofluoroscopy. Children with GER presented alteration in clinical evaluations on 64,9% (n=24) and the control group on 13,3% (n=2), swallowing less diet solid diet, presents nausea, feeding refusal, choking and irritation. Videofluoroscopy evaluation for liquids, showed laryngeal penetration on 61,8 % (n =21) , GC 33,3% (n=5), and backward compensatory movement in 64,7% (n=22) e GC 0%, it was similar for the semi-solid diet 41,2% (n=14) e GC (n=0). There was no difference in time of the swallowing phases. This study shows that children with GER present difficulties to accepting feeding although no alteration on the oropharyngeal dynamics timing of swallowing was founded.