L'ingestion de nourriture entraîne l'activation neuronale dans des régions spécifiques du cerveau qui sont responsables de l'intégration d'une panoplie de signaux postprandiaux, incluant ceux induits par les hormones gastro-intestinales et celles impliquées dans la régulation de la balance énergétique et hydrique de l'organisme. Les mécanismes et les voies par lesquelles les hormones digestives agissent au cerveau afin d'exercer leurs effets sur la prise alimentaire ne sont pas encore éclaircis. Les travaux présentés dans cette thèse visaient à i) examiner l'activation neuronale cérébrale induite par le repas et particulièrement par deux hormones intestinales, le glucagon-like peptide 1 (GLP-1) et le peptide YY (PYY) et ii) mettre en évidence les rôles respectifs du nerf vague et des organes circumventriculaires (CVOs) dans la transmission des signaux digestifs postprandiaux au niveau cérébral. Nous avons observé que l'ingestion de nourriture entraîne l'expression de l'ARNm de c-fos (un marqueur d'activité neuronale) dans des régions spécifiques du cerveau incluant des noyaux de l'hypothalamus, du thalamus, des structures limbiques, du tronc cérébral et des CVOs. L'activation du système GLP-1 déclenche une stimulation dans plus ou moins les mêmes zones que le repas mais selon un patron d'intensité différent. L'activation neuronale dépendante de PYY est restreinte à des noyaux tronculaires et limbiques. Nous avons utilisé des modèles d'ablation des voies vagales et des CVOs, afin d'évaluer leur rôles respectifs dans l'activation neuronale induite par le repas, par le GLP-1 et par le PYY. Nous avons observé que la stimulation des régions du tronc cérébral (le noyau du tractus solitaire et le noyau parabrachial) et des neurones parvocellulaires du noyau paraventriculaire de l'hypothalamus (PVHp) est dépendante de l'intégrité du nerf vague et de l'area postrema. L'activation des neurones magnocellulaires hypothalamiques semble être plutôt déclenchée par des signaux postpradiaux entrant dans le cerveau via les CVOs frontaux, tels l'organe sous-fornical et l'organe vasculaire de la lame terminale. D'autres régions hypothalamiques incluant la partie médio-dorsale du PVHp et le noyau arqué, ainsi que les structures limbiques sont influencées par les deux voies, systémique et vagale. Si l'intégrité des CVOs ne semble pas être essentielle à l'action inhibitrice du GLP-1 sur la prise alimentaire, elle l'est en partie sur leffet anorexigène du PYY qui semble dépendre à la fois des CVOs et de la voie vagale.

Les systèmes d'élevage des petits ruminants au pâturage sont les plus répandus en zone tropicale humide mais l'exposition aux strongles gastro-intestinaux entraîne des pertes importantes de production. L'objectif de ce travail est d'évaluer un système de gestion mixte du pâturage associant diverses espèces animales permettant à priori d'accroître les performances via la réduction du parasitisme et!ou une meilleure alimentation. L'étude de la littérature a conduit à une méta-analyse confirmant de meilleures performances individuelles ou à l'hectare pour les ovins en mixte. Préalablement un dispositif visant à vérifier la non-transmission des larves d'Haemonchus contortus des caprinsaux génisses Créoles a été validé. Un second dispositif avec des chevrettes conduites en mixte, infestées ou pas par Haemonchus comortus (Ml et MnI) ont été comparées à des chevrettes contrôles infestées ou non (CI et CnI). Ce dispositif a été conduit pendant 2 ans avec des mesures du couvert pâturé, des mesures individuelles des quantités ingérées, de la digestibilité, du parasitisme et de la croissance. De plus fortes croissances ont étéobservées en pâturage mixte que les chevrettes soient infestées ou pas (43.25 et 31.68 glj pour MDI et MI vs. 32.44 et 17.91 glj) avec une moindre biomasse. Les mesures d'ingestion et d'ingéré digéré ont été corrélées aux croissances des chevrettes contrairement aux variables parasitaires et met en évidence le rôle de l'alimentation et de la résilience dans le bénéfice du pâturage mixte. Une autre gestion intégrée du pâturage a été étudiée basée sur l'utilisation du vermicompost et s' ant sur les mêmes leviers d'action: l'alimentation et le itisme / Systems of small ruminant grazing are most prevalent in the humid tropics but this environment exposes animals to gastro-intestinal with production losses. The objective ofthis thesis is to evaluate a system ofmixed management ofthe pasture combining various animal species, which allows a priori to increase animal performance by reducing the parasitism and/or better nutrition. The study of literature bas led to a meta-analysis confirming the better individual performances or calculated per ha for sheep reared mixed. The first experiment validated the non-transmission of Iarvae ofHaemonchus contortus from goats to heifers. In a second experiment, goats mixed with heifers, infested or not with Haemonchus contortus (Ml vs MnI) were compared with controls goats, reared alone, infested or not (CI and CNI). This deviee with a continuous driving was studied for two years with measurements on the sward, individual measures of intake, digestibility, parasitism and growth ofthe goats. The highest growth rates were measured with the mixed pasture as goats are infested or not (43.25 and 31.68 g / d for MN! and MI vs. 32.44 and 17,91 g / d) with lower biomass. The herbage intake and the digested herbage intake were well correlated to the growth rate, unIike parasitic variables, and highlight the role of diet in the benefit of mixed driving for goats. Therefore, the infested goats with Haemonchus, expressed greater resilience with improved growth performance compared with controls. Parallel to the study ofmixed pasture, another integrated management of grazing was studied, based on the use of vermicompost and relying on the same levers. namelv throuzh feedinz and parasitism

Les procédures gastro-intestinales de l’oesophage impliquent un contrôle ou une surveillance périodique de l'anatomie interne (réalisation de multiples biopsies le long de l’oesophage). Le suivi et la relocalisation inter-opératoires de ces sites de biopsies (pour un même patient opéré plusieurs fois) est un challenge bien connu. L'objectif de cette thèse est de proposer une solution informatisée afin de guider le gastroentérologue pendant de telles procédures. Nous proposons un cadre novateur utilisant un système de suivi électromagnétique pour réaliser des enregistrements d'intervention de l’oesophage, couplant la vidéo à la profondeur de l'endoscope inséré. Ces enregistrements sont ensuite utilisés afin de repositionner l'endoscope de façon précise sur des sites de biopsie préalablement ciblés. Cette navigation consiste en une synchronisation vidéo entre la vue endoscopique courante et celles des surveillances endoscopiques précédentes enregistrées. Une première version de notre système est évaluée de manière incrémentale sur des données d'abord synthétiques puis réelles recueillies sur des cochons. Les résultats montrent que la relocalisation est obtenue avec une précision de l'ordre de 10mm, considérée comme largement acceptable par les experts. En outre, une expérience qualitative simulant une tâche réelle de relocalisation de site de biopsie, évaluée par 10 gastroentérologues, démontre les avantages du système de guidage assisté. Ce cadre est finalement étendu afin d'améliorer encore la précision de la relocalisation à partir d'une sélection optimale de l'image vidéo pré-enregistrée dont le point de vue est le plus proche de celui de l'image endoscopique courante / Gastrointestinal (GI) procedures, specifically, oesophageal interventions involve periodic monitoring or surveillance of the internal anatomy, which involve obtaining biopsies at different regions along the oesophagus. The tracking and relocalization of these biopsy sites ``inter-operatively'' poses a significant challenge for providing targeted treatments. This thesis, clarifies the concept of relocalization, and analyses the need for a platform to aide GI endoscopy. Based on the understanding of the clinical context in oesophageal procedures; a novel framework to use electromagnetic tracking system is proposed, which is used to perform a ``recording'' of an intervention. This framework and the recording is then used to provide a guided navigation to the GI expert, during a follow-up surveillance endoscopy; for accurate re-positioning of the endoscope at previously targeted sites. This is achieved using inter-operative video synchronization, and the various steps involved in achieving this are described in this thesis. A careful analysis of noise affecting the system is performed, to propose quantitative analysis using synthetic and realdata collected on pigs. A set of qualitative experiments were also proposed using 10 experts to indicate benefit to the GI community. The quantitative experiment indicated that the relocalization was achieved with an accuracy of 10mm, and the qualitative experiments showed that the biopsy site relocalization rate improved from 47.5% to 94%. The thesis then proceeds to provide two additional improvements using additional information collected during the GI intervention for a complete solution

Résumé: Introduction : Le rotavirus est la principale cause de gastro-entérite aiguë (GEA) chez les tout-petits à travers le monde. En 2011, le vaccin antirotavirus monovalent (RV1) a été introduit dans le programme de vaccination universel du Québec afin de réduire la morbidité reliée à la gastro-entérite à rotavirus (GERV). Ce mémoire avait pour objectif de décrire les taux d’hospitalisation pour GEA et GERV avant et après l’implantation du programme chez les jeunes enfants estriens (étude d’impact) ainsi que la couverture vaccinale et d’évaluer l’efficacité vaccinale (EV) du RV1 (étude d’efficacité). Méthode : Le jumelage d’une banque de données hospitalières avec le registre régional de vaccination a permis d’extraire une cohorte d’enfants nés au Centre hospitalier universitaire de Sherbrooke (CHUS), vivant en Estrie et âgés de moins de cinq ans durant la période d’étude de juin 2004 à mai 2014 (n = 37 757). Cette cohorte a été suivie de façon rétrospective afin d’examiner les taux annuels d’hospitalisation pour GEA et GERV des années pré- (2004/2005-2010/2011) et post-implantation (2011/2012-2013/2014), globalement et selon diverses caractéristiques socioéconomiques. De plus, l’EV du RV1 a été calculée à l’aide de trois cohortes d’enfants : (1) les enfants vaccinés nés en 2011-2013 (n = 5 033), (2) les enfants non vaccinés nés en 2011-2013 (n = 1 239) et (3) les enfants non vaccinés nés en 2008-2010 (n = 6 436). Résultats : Le taux d’hospitalisation pour GEA a évolué de 81/10 000 enfants de moins de cinq ans en période pré-implantation à 46/10 000 en période post-implantation (réduction relative = 43 %, p < 0,001). Suite à l’implantation du programme, la couverture vaccinale a rapidement augmenté pour atteindre 81 %. Malgré une couverture vaccinale similaire parmi les différents groupes, les plus faibles réductions relatives ont été observées chez les groupes défavorisés. L’EV ajustée pour une série complète était de 62 % (intervalle de confiance [IC] 95 % : 37-77 %) et de 94 % (IC 95 % : 52-99 %) contre les hospitalisations pour GEA et GERV, respectivement. Les enfants vivant dans des quartiers ayant une proportion élevée de familles à faible revenu avaient une EV plus faible contre les hospitalisations pour GEA (30 % contre 78 %, p = 0,027). Conclusion : Trois ans après son introduction dans le programme universel, le RV1 a réduit de façon significative les gastro-entérites sévères chez les jeunes enfants estriens. Ce vaccin est très efficace pour prévenir les hospitalisations pour GERV, particulièrement chez les groupes plus aisés. D’autres études en contexte similaire sont nécessaires pour déterminer les facteurs reliés à une plus faible EV chez les groupes vulnérables. / Abstract: Introduction: Rotavirus is the main cause of acute gastroenteritis (AGE) among young children worldwide. In 2011, the monovalent rotavirus vaccine (RV1) was introduced into the Quebec universal immunization program to reduce morbidity related to rotavirus gastroenteritis (RVGE). This thesis aimed to examine AGE and RVGE hospitalization rates before and after implementation of the program in young children from the Eastern Townships (impact study) and the vaccine coverage, and to assess vaccine effectiveness (VE) of the RV1 (effectiveness study). Methods: The pairing of a tertiary hospital database with the regional immunization registry allowed to extract a cohort of children born at the Centre hospitalier universitaire de Sherbrooke (CHUS), living in Eastern Townships and aged less than five years during the study period from June 2004 to May 2014 (n= 37,757). This cohort was retrospectively followed-up to examine AGE and RVGE annual hospitalization rates of pre- (2004/2005-2010/2011) and post-program years (2011/2012-2013/2014), globally and according to several socioeconomic characteristics. Moreover, RV1 VE was calculated using three children cohorts: (1) vaccinated children born in 2011-2013 (n=5,033), (2) unvaccinated children born in 2011-2013 (n=1,239), and (3) unvaccinated children born in 2008-2010 (n=6,436). Results: AGE hospitalization rates evolved from 81/10,000 children aged less than five years in pre-program period to 46/10,000 in post-program period (relative reduction=43%, p<0.001). Following implementation of the program, vaccine coverage rapidly increased to reach 81%. Despite similar vaccine coverage among different groups, lowest relative reductions were observed in disadvantaged groups. Adjusted VE of a complete series was 62% (95% confidence interval [CI]: 37%-77%) and 94% (95% CI: 52%-99%) against AGE and RVGE hospitalizations, respectively. Children living in neighbourhoods with higher rates of low-income families had lower VE against AGE hospitalizations (30% vs. 78%, p=0.027). Conclusion: Three years following its introduction into the universal vaccination program, RV1 significantly reduced severe gastroenteritis in young children in the Eastern Townships. This vaccine was highly effective to prevent RVGE hospitalizations, particularly among the most well-off. Further studies in similar setting are needed to determine factors related to lower VE among vulnerable groups.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Gastro wastes, as a sort of biodegradable waste, has been established in legislation just quite recently, and its sorting is just in the beginning. However as a sort of waste it has a great potential like a secondary material. This work deals with gastro waste modelling and optimization of their cartage routes with purpose to decrease negative implications with them connected. For the model composition, the operational research was used, namely the transportation task or the circular transportation problem, further optimization (that includes the linear optimization and the index method.) The program ArcGIS and its extension Network Analyst from ERSI were used for delineation of transportation routes. Microsoft Excel, Visual Basic and Python were used for computation of optimization tasks. Final graphic output was carried out in the ArcGIS ArcMap. The results of this work are optimized trucking cartage routes, calculated values of minimal distances, quantity of cartage cars, calculated overall costs and other calculations. The part of this tasks is also time conversion of the model. Also, the attention was paid for minimization of trucking routes. The increase of the capacity of specific gastro waste processors was used for the minimization. These processors were chosen in accordance with required...

Faculty of Health Scicence School of Medicine 0100107g johannes.geyer@wits.ac.za / The 14C and 13C labelled urea breath tests (UBT) for detecting Helico-bacter pylori infection are well established but scope for improvement exists in both to reduce some of their shortcomings. For this study, the 14C UBT investigation focussed on reducing the quantity of radioactive tracer that is administered to the subject un-dergoing this test, with the aim of lowering the radiation dose to the patient, reducing the impact to the environment and exempting the test from radioactive materials licensing. Wider acceptance, availabil-ity, affordability to lower socio-economic groups and third party medi-cal treatment payers and using readily available equipment were fac-tors considered when developing the method. The principle of the method developed is to collect larger volume breath sample, quantitatively absorbing a defined volume of extracted breath CO2 in an efficient CO2 trapping agent using a specifically de-signed apparatus and measuring the activity with a low background β-spectrometer. A reduction in the quantity of 14C labelled urea administered to the pa-tient was achieved. The method also reduced the counting error mar-gin at a lower detection limit, improving discrimination between H. py-lori positive and negative patients. iii The 13C UBT is a non-radioactive test however, it is substantially more expensive. The 13C UBT investigation aimed to determine whether commercially available un-enriched urea could be used thus reducing the cost of the 13C UBT. A simple protocol with Isotope Ratio Mass Spectrometry (IRMS) for the measurement was used as opposed to the well-established 13C UBT protocol. The principle of the 13C UBT investigation was to detect the change of the breath δ13C (13C/12C) ratio after the administration of un-enriched urea with a δ13C different to the exhaled breath. Theoretical calculations showed that an administered dose of 500mg un-enriched urea with at least a 10‰ δ13C difference may be detectable using IRMS. In vitro investigations confirmed that levels of 0.01 to 0.001‰ δ13C were detectable by IRMS. A change in the δ13C of a standard breath CO2 was confirmed for a range between 0.14 to 50% v/v mixed CO2 samples, i.e. the projected range for in-vivo investigation. Results from the in-vivo investigation however were not able to distinguish positive from negative H. pylori patients. The use of the 1000mg dose of urea appears to have caused saturation of the enzyme. It was con-cluded that some enrichment of the 13C is necessary or less urea be used.

Background: 20 to 30% of patients with GORD respond inadequately to conventional therapy. Most of these patients belong to the non-­‐erosive reflux disease group. Despite not having oesophagitis, in these patients oesophageal mucosal integrity appears to be impaired. Aims: To study the dynamic in vitro and in vivo properties of oesophageal mucosal integrity in patients with non-­‐erosive reflux disease, and to test the feasibility of a topical mucosal protectant therapy. Methods: In vitro studies of mucosal integrity were done on human oesophageal biopsies using Ussing chambers. Change in transepithelial electrical resistance (TER) on exposure to acidic solutions was measured. Integrity was assessed in vivo by measuring impedance change and subsequent recovery after oesophageal acid perfusion in symptomatic patients. Proximal and distal oesophageal mucosal integrity was assessed in vitro and in vivo. The effect of in vitro topical application of an alginate-­‐based solution on acid-­‐induced changes in mucosal integrity was tested. Results: In vitro exposure of biopsies to acidic and weakly acidic solutions caused a greater impairment of integrity in symptomatic patients than in controls. In vivo oesophageal acid perfusion causes a profound drop in distal oesophageal impedance that is slow to recover. Recovery is slower in patients with non-­‐erosive reClux disease than in patients with functional heartburn, and a low baseline impedance is associated with painful perception of acid. Proximal oesophageal sensitivity appears unrelated to impaired mucosal integrity, but rather to a distinct sensory afferent nerve distribution. Topical pre-­‐treatment with an alginate solution is able to prevent acid-­‐induced changes in integrity in vitro. Conclusion: Patients with non-­‐erosive reClux disease have a distinct mucosal vulnerability to acidic and weakly acidic solutions that may underlie persistent symptoms. A topical therapeutic approach may be a feasible add-­‐on strategy to treat GORD in the future.

Thesis (M.Pharm. (Pharmaceutics) -- University of Limpopo, 2018 / Griseofulvin is an antibiotic fungistatic drug used in the treatment of dermatophyte and ringworm infections. About 50% of a dose of griseofulvin passes the gastro- intestinal tract unabsorbed and is excreted in faeces. Since griseofulvin is highly soluble in acidic pH, a gastro-retentive floating matrix system was developed to control dissolution rate and thereby enhance solubility in an effort to develop an improved and convenient dosage form. Preformulation studies included selection of excipients and evaluation of their compatibility with griseofulvin. Using the chosen excipients, floating tablets of griseofulvin were formulated. Floating tablets containing 100 mg of griseofulvin were prepared by wet granulation technique with varying ratios of Methocel™, Accurel MP and Polyvinylpyrrolidone as determined by Design Expert software. Pre and post-compression studies, buoyancy capability and dissolution studies were carried out to assess the influence of the tablet components. Results obtained revealed that a density of less than 0.00091 g/cm3 was necessary for tablet floatation. Tablets that float immediately upon contact with dissolution medium and continue floating for over 12 hours were achieved with at least 28% Accurel MP by mass of the tablet. Dissolution studies revealed that an increase in tablet hardness reduced the rate of griseofulvin release only up to 120 minutes. From 120 minutes onwards, tablet hardness had no significant influence on griseofulvin release from tablets. Methocel™ had the most significant influence on griseofulvin release. The amount of Methocel™ included in the formulation was indirectly proportional to the rate of griseofulvin release. Using Design Expert software, optimized formulation was achieved with 1% Polyvinylpyrrolidone, 30% Methocel™, 60% Accurel MP and hardness ranging between 8 – 9 N. Pre and post-compression parameters of the optimized tablets were found to be within pharmacopoeial limits and thus compressed tablets were of acceptable quality. Tablets produced floated immediately upon contact with the medium and remained floating for at least 12 hours. Griseofulvin was released from the optimized tablets in a near zero order fashion, with a total of 80.8% griseofulvin released at the end of the 12 hour dissolution test period. Results of accelerated stability studies indicated potential stability of the manufactured tablets months.

One of the aims included in the United Nations Millennium Development Goals is to decrease the number of the world’s population without access to sanitation and water that is safe, by half by the year 2015. The use of water that is not safe for consumption leads to water–related diseases. For the purpose of this study gastro–intestinal disease was redefined as diseases of the gastro–intestinal tract caused by pathogens that spread via contaminated drinking water, poor sanitation and inadequate hygiene. Information obtained regarding the use of gastro–intestinal disease medication, may provide information about the prevalence of gastro–intestinal disease in South Africa. The general objective of this study was to determine the prescribing patterns of gastro–intestinal medication in different geographical areas in the private health care sector of South Africa. A retrospective drug utilisation review was conducted on data obtained from a medicine claims database of a pharmacy benefit management company for 2007 and 2008. A pharmacoepidemiological approach was followed in order to determine the prevalence of gastro–intestinal disease as well as the use of gastro–intestinal medication in South Africa as well as the different provinces of South Africa. The impact of water quality and sanitation on the prevalence of gastro–intestinal disease was also investigated. Gastro–intestinal medication (used in the treatment of gastro–intestinal disease) included the following pharmacological groups according to the MIMS®–classification: antivertigo and anti–emetic agents (group 1.8), antispasmodics (group 12.3), antidiarrhoeals (group 12.7), minerals and electrolytes (group 20.4, selected according to specified NAPPI–codes) and antimicrobials (group 18). Antimicrobials had to be prescribed in combination with one of the specified gastro–intestinal medication groups in order to be classified as a gastro–intestinal medication. In 2007 and 2008 respectively, 428864 and 340921 gastro–intestinal medication items were prescribed. The most frequently prescribed gastro–intestinal medication pharmacological groups in 2007 and 2008 were beta–lactam antimicrobials (with proportion percentages of 22.77% and 20.85% in 2007 and 2008 respectively), antivertigo and anti–emetic agents, antispasmodics, antidiarrhoeals and quinolone antimicrobials. Minerals and electrolytes represented only a small proportion (2.99% and 2.56% in 2007 and 2008 respectively) of the prescribed gastro–intestinal medication in South Africa. In the Free State and Western Cape antivertigo and anti–emetic agents were the most frequently prescribed gastro–intestinal medication items, while in other provinces beta–lactam antimicrobials ranked the highest. In all provinces except the Western Cape and the Northern Cape, amoxicillin/clavulanic acid was the most frequently prescribed gastro–intestinal medication active ingredient. In the Western Cape loperamide was the most frequently prescribed active ingredient, while ciprofloxacin ranked highest as active ingredient in the Northern Cape in 2008. Based on the prescribing patterns of gastro–intestinal disease medications the treatment of gastro–intestinal disease in this section of the private health care sector of South Africa, does not fully comply with the Standard Treatment Guidelines with regard to the use of antimicrobials and electrolyte replacement therapy. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.