Les tumeurs gastro-intestinales stromales (Gastro-Intestinal Stromal Tumours - GIST en Anglais) sont les sarcomes les plus fréquents du tube digestif. Sur base de leur profil d'expression génique et de similitudes morphologiques, il a été établi que les GIST dérivent des cellules interstitielles de Cajal (Interstitial Cells of Cajal - ICC en Anglais) ou d'un précurseur commun. Le développement et le maintient des ICC sont dépendant de voies de signalisation du récepteur tyrosine kinase KIT. Des mutations oncogéniques de KIT, conduisant indépendamment du ligand à l'activation des voies de signalisation en aval, sont présentes dans environ 85% des GIST. Depuis une dizaine d'années, des molécules de synthèse qui inhibent la phosphorylation -et donc l'activation - de KIT ont été introduites avec succès dans le traitement clinique des GIST. Cependant des résistances, souvent causées par des mutations secondaires, apparaissent fréquemment et environ 50% des patients traités rechutent dans les 2 ans. Le développement de nouvelles stratégies diagnostiques et thérapeutiques pour les GIST demeure donc essentiel. Ces dernières années, de nouveaux marqueurs diagnostiques ou cibles thérapeutiques potentielles ont été rapportés dans la littérature (p.ex. Discovered on GIST-1 (DOG1, anoctamin 1), Protein kinase C theta (PKC theta), Carbonic anhydrase II (CAII)) .Il faut relever que tous ces gènes sont aussi exprimés par les ICC KIT+ du tube digestif normal et que leur présence dans les GIST reflète donc vraissemblablement essentiellement leur parenté avec les ICC.<p>Dans la présente étude, nous nous sommes attachés à identifier de nouveaux marqueurs diagnostiques ou cibles thérapeutiques potentielles exprimés par les GIST mais absent des ICC KIT+ normales.<p>Pour ce faire, nous avons comparé le profile d'expression géniques de l'antre gastrique de souris porteuses de la mutation oncogénique Kit K641E et de souris contrôles (wild type WT en Anglais) par la technique de cDNA microarray. Les différences d'expression génique ont été ensuite confirmées par réactions de PCR quantitative (qPCR) en temps réel et l'immunoréactivité (-ir) pour les candidats les plus prometteurs a été localisée par immunofluorescence (IF) dans la muscularis propria du tube digestif, avec une attention spéciale pour les cellules KIT+.<p>Plusieurs gènes identifiés appartenaient tant au profil d'expression génique des GIST qu'au profil d'expression des ICC Kit+ de l'intestin grêle murin, validant ainsi la pertinence du modèle murin KitK641E pour l'approche choisie (Chapitre 3). D'autre part, trois gènes identifiés (Neurotensin receptor 1 (Ntsr1), Trophoblast glycoprotein (Tpbg/5T) et Sprouty homolog 4 (Spry4)) étaient quant à eux présents dans la couche hypertrophié de cellules Kit+ de l'antre des souris KitK641E mais absentes des ICC Kit+ chez les souris WT (Chapitres 3, 4, 5). Ces gènes représentant donc de nouveaux candidats potentiels comme marqueurs spécifiques et/ou comme cibles thérapeutiques dans les GIST, nous avons, dans la seconde partie de notre travail, approfondi l'étude de leur expression et de leur régulation en utilisant des modèles cellulaires et tissulaires murins, ainsi que du matériel anatomopathologique de GIST humains.<p>Dans le tube digestif normal, NTSR1 et TPBG/5T4 ir ont été identifiés dans les neurones myentériques mais pas dans les ICCKIT+. Deux "tissue arrays" indépendants, totalisants 97 spécimens humains de GIST, ont révélés la présence de NTSR1-ir dans tous les GIST, en ce compris les cas négatifs pour KIT, tandis que TPBG/5T4-ir était présente dans 36/49 GIST. Un fort immunomarquage pour TPBG/5T4 était statistiquement associée aux tumeurs malignes et de haut risque (Chapitre 5; Annexe 1).<p>L'expression différentielle de membres de la famille des "Sprouty homologues" (Spry) dans l'antre des souris KitK641E a aussi été identifiée. Spry4-ir n'était pas détectable dans les ICC KIT+ des souris WT alors que Spry4-ir était présente dans la couche hyperplasique des cellules Kit+ chez les souris KitK641E. A l'opposé, l'ARN messager de Spry2 présentait un niveau d'expression similaire et Spry2-ir était détectée dans les cellules musculaires lisses - mais pas dans les cellules Kit+ - dans tous les génotypes (Chapitre 3). Pour sa part, l'expression de Spry1 apparaissait réprimée par le mutant oncogénique KitK641E, tant in vivo qu'in vitro, conduisant à la dérégulation de la boucle de rétrocontrôle négatif de la voie Ras/Erk (Chapitre 4). <p>Dans la dernière partie de cette thèse, nous avons étudié l'expression Endoglin (ENG) - aussi connues sous le nom de CD105 – dans le modèle murin de GIST KitK641E, dans les GIST humains et dans le modèle cellulaire murin Ba/F3 in vitro. ENG est une glycoprotéine transmembraire et un composant auxiliaire du complexe du récepteur au TGF-& / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

M.Sc. (Pharmaceutical Affairs), Faculty of Health Sciences, University of the Witwatersrand, 2009

Actuellement, 70 % de la population mondiale est concernée par la baisse génétiquement programmée de l’activité de la lactase. Pour ces sujets, la consommation de lactose peut entrainer de sévères troubles digestifs. Les produits diététiques étudiés, réhydratés à l’aide de lait par le consommateur, sont donc potentiellement source d’inconforts. La première partie de ce projet s’est par conséquent attachée à développer des moyens permettant l’obtention de produits convenant à la majorité de la population intolérante au lactose. Dans le même temps, de plus en plus conscient du lien étroit liant alimentation, santé et bien être, le consommateur tend depuis quelques années à modifier ses habitudes alimentaires. Cela se traduit par un intérêt grandissant pour les aliments « santé ». La formulation de tels produits se heurte toutefois encore au manque de connaissances quant à la biodisponibilité de certains macro et micronutriments. Ce projet à visée industrielle propose par conséquent d’optimiser la digestibilité de l’amidon et des protéines contenus dans différents produits diététiques destinés à remplacer l’intégralité de la ration journalière. Pour ce faire, la digestibilité de différentes sources d’amidon (blé, maïs, maïs cireux, manioc, pomme de terre, riz et riz cireux) et de différentes protéines (caséines, concentrat de protéines de lait, isolat de protéines de pois, poudre de blanc d’œuf, concentrat de protéines sériques et isolat de protéines de soja) a été étudiée in vitro et comparée / Currently, 70% of the world population is affected by the genetically programmed decline in lactase activity. For these subjects, lactose consumption can cause severe digestive disorders. The studied dietetic products, usually rehydrated with milk by the consumer before use, are hence a potential source of digestive discomfort. The first part of this project deals therefore with development ways in order to obtain suitable products for the majority of lactose intolerant population. Laterraly, increasingly aware of the close link between food and health, consumers tend to change their eating habits. This is reflected by a growing interest in "healthy" foods. The formulation of these products is however still hampered by a lack of knowledge about some macro and micronutrients bioavailability. This industrial project aims to maximize the digestibility of starch and protein contained in dietary products replacing the entire daily ration. The digestibility of different starch sources (wheat, corn, waxy maize, cassava, potato, waxy rice and rice) and different food proteins (caseins, milk protein concentrate, pea protein isolate, egg white powder, whey protein concentrate and soya protein isolate) has thus been studied and compared in vitro

No description available.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for systemic control of acute and chronic pain and inflammation (Lin et ah, 2000:1129), but usage problems and side-effects that occur during the post-marketing phase of these drugs are well documented (Thiefin & Beaugerie, 2005:287). Following the demonstration of the value of anti-inflammatory therapy in diseases like rheumatoid arthritis (Boardman & Dudley Hart, 1967:268), new NSAIDs appeared on the market (Dieppe et al., 2004:867), and the indications steadily broadened from inflammatory diseases to almost any painful condition. Studies have indicated that NSAID-associated serious upper gastro-intestinal (GI) adverse events result in 103 000 hospitalisations (Bombardier, 2002:4) and 165 000 deaths per year in the United States. A study in South Africa in 2002 indicated that NSAID utilisation contributed considerably to the total cost of all medicine items from a medicine claim database in the private health care sector (Joubert, 2002:260). The objective of this study was to determine the prevalence and cost of non-steroid anti-inflammatory drugs in a section of the private health care sector, and specifically to determine the prevalence, usage and cost of Coxib (Specific cyclo-oxygenase-2 inhibitor) medicine items before and after the withdrawal of Vioxx® from the market in September 2004 (Merck, 2004). Data from two medicine claim databases for the years 2004, 2005 and 2006 (medicine claim database I) and the years 2005 and 2006 (medicine claim database M), were analysed by means of a retrospective drug utilisation review (DUR) study. The usage of Coxib medicine items was determined, and compared for the periods before and after the withdrawal of Vioxx® in September 2004. It was found that between 9 and 10.5 per cent of prescriptions dispensed through both medicine claim database I and medicine claim database M during the study period were NSAID prescriptions. NSAID medicine items on medicine claim database I represented between 3.9 % (R25 942 986) and 2.9 % (R8 073 034) of the total cost of all medicine items claimed from 2004 to 2006. NSAIDs represented 3.1 % (R58 290 412) and 2.8 % (R57 752 267) of the cost of all medicine items claimed through medicine claim database M during 2005 and 2006 respectively, indicating similar trends in the two medicine claim databases. The prevalence of Coxibs on medicine claim database I decreased from almost 20 % (47 938) in 2004 to 8.4 % (13 276) in 2005, but showed an increase again to 10.9 % (12 355) in 2006. The prevalence of both cyclo-oxygenase (COX) inhibitors, and Coxibs demonstrated a change during 1 September 2004 to 31 December 2004 when COX-inhibitors showed an increase in use, while Coxibs showed and almost equal but opposite trend with a decrease in use. This could possibly be related to perceptions of providers and public with regard to Coxibs and their related safety after the withdrawal of Vioxx® on 30 September 2004 (Merck, 2004) and other Coxibs such as Bextra® (FDA, 2005) in 2005 in USA. It is concluded that most patients who were using Coxibs before the withdrawal of Vioxx®, substituted Coxibs for COX-inhibitors, that are known for their possible gastro-intestinal side-effects. Recommendations for future research regarding NSAID use were also made, and included an investigation of the usage of Coxibs in different age groups, as well as the combination of NSAIDs with gastro-protective medicines in long-term use. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2009.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for systemic control of acute and chronic pain and inflammation (Lin et ah, 2000:1129), but usage problems and side-effects that occur during the post-marketing phase of these drugs are well documented (Thiefin & Beaugerie, 2005:287). Following the demonstration of the value of anti-inflammatory therapy in diseases like rheumatoid arthritis (Boardman & Dudley Hart, 1967:268), new NSAIDs appeared on the market (Dieppe et al., 2004:867), and the indications steadily broadened from inflammatory diseases to almost any painful condition. Studies have indicated that NSAID-associated serious upper gastro-intestinal (GI) adverse events result in 103 000 hospitalisations (Bombardier, 2002:4) and 165 000 deaths per year in the United States. A study in South Africa in 2002 indicated that NSAID utilisation contributed considerably to the total cost of all medicine items from a medicine claim database in the private health care sector (Joubert, 2002:260). The objective of this study was to determine the prevalence and cost of non-steroid anti-inflammatory drugs in a section of the private health care sector, and specifically to determine the prevalence, usage and cost of Coxib (Specific cyclo-oxygenase-2 inhibitor) medicine items before and after the withdrawal of Vioxx® from the market in September 2004 (Merck, 2004). Data from two medicine claim databases for the years 2004, 2005 and 2006 (medicine claim database I) and the years 2005 and 2006 (medicine claim database M), were analysed by means of a retrospective drug utilisation review (DUR) study. The usage of Coxib medicine items was determined, and compared for the periods before and after the withdrawal of Vioxx® in September 2004. It was found that between 9 and 10.5 per cent of prescriptions dispensed through both medicine claim database I and medicine claim database M during the study period were NSAID prescriptions. NSAID medicine items on medicine claim database I represented between 3.9 % (R25 942 986) and 2.9 % (R8 073 034) of the total cost of all medicine items claimed from 2004 to 2006. NSAIDs represented 3.1 % (R58 290 412) and 2.8 % (R57 752 267) of the cost of all medicine items claimed through medicine claim database M during 2005 and 2006 respectively, indicating similar trends in the two medicine claim databases. The prevalence of Coxibs on medicine claim database I decreased from almost 20 % (47 938) in 2004 to 8.4 % (13 276) in 2005, but showed an increase again to 10.9 % (12 355) in 2006. The prevalence of both cyclo-oxygenase (COX) inhibitors, and Coxibs demonstrated a change during 1 September 2004 to 31 December 2004 when COX-inhibitors showed an increase in use, while Coxibs showed and almost equal but opposite trend with a decrease in use. This could possibly be related to perceptions of providers and public with regard to Coxibs and their related safety after the withdrawal of Vioxx® on 30 September 2004 (Merck, 2004) and other Coxibs such as Bextra® (FDA, 2005) in 2005 in USA. It is concluded that most patients who were using Coxibs before the withdrawal of Vioxx®, substituted Coxibs for COX-inhibitors, that are known for their possible gastro-intestinal side-effects. Recommendations for future research regarding NSAID use were also made, and included an investigation of the usage of Coxibs in different age groups, as well as the combination of NSAIDs with gastro-protective medicines in long-term use. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2009.

INTRODUCTION: Cancers of the gastrointestinal tract are the second most prevalent malignancy with 289,610 new cases last year and the second most common cause of cancer-related death with 150,000 deaths last year in the United States. Prognosis for patients with these malignancies is poor and worsens significantly once the cancer has metastasized to the brain. We evaluated the outcome of patients following Stereotactic Radiosurgery (SRS) for brain metastases (BM) in individuals with GI cancers to identify safety and effectivity of treatment and we assessed prognostic factors that affect tumor control and survival. OBJECTIVES: By the conclusion of this session, participants should be able to: 1) Identify an effective treatment for brain metastases from GI cancers in terms of increasing survival; 2) Identify which treatment provides the best local and distant control of CNS disease; 3) Discuss the effects of different prognostic factors on local control and survival. METHODS: This is a retrospective analysis of 58 brain metastases from 18 consecutive patients who underwent SRS treatment at BIDMC between 2006 and 2013. 11/18 patients underwent prior microsurgical resection for their metastases and 3/18 patients had undergone Whole Brain Radiation Therapy (WBRT). Overall Survival (OS), Local Control (LC), Distal control (DC), and prognostic factors such as age, number of brain metastases (BM), Karnofsky Performance Status (KPS), Recursive Partition Analysis (RPA) and Disease Specific Graded Prognostic Assessment (Ds-GPA) class were evaluated. RESULTS: The median overall survival (mOS) for the entire cohort was 14 months after the diagnosis of BM. The mOS for patients receiving only SRS, Surgical Resection + SRS, and WBXRT + SRS were 8 months, 18 months, and 13 months respectively. The difference in overall survival between treatment groups was not found to be statistically significant. Increasing number of BM was a factor shown to negatively influence survival. Local control was achieved in 55% of lesions after SRS, and in 75% of lesions that were surgically resected followed by SRS boost to the resection cavity. The difference in local control between SRS alone vs. Surgery + SRS was found to be statistically significant (p = 0.013). CONCLUSION: With a higher overall survival and significantly better local control rates, Surgery followed by SRS boost to the resection cavity should be considered as the treatment of choice in this specific subgroup of cancer patients as this study shows that they benefit from this more aggressive treatment option.

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

No description available.

Thesis(M. A. Agricultural Management (Animal Production)) -- University of Limpopo, 2019 / The study was conducted to assess phenotypic and genotypic diversity in resistance to gastro-intestinal nematode (GIN) within communal goats in different agro-ecological zones of Limpopo province. Eighty goats were randomly sampled from Mopani = 20, Blouburg = 20, Vhembe = 20 and Capricorn = 20, representing four agro-ecological zones of Limpopo province. Frequencies and percentages of occurrence of qualitative traits and least square means (LSM) of quantitative traits were computed. Goats were characterized as multi-coloured (67.7%), black dominant coat colour (40%), flat face profile (73.8%), erect ears (68.75%), slopping rump (47.5%), no toggles (83.8%), horned (86.3%), while 71.0% and 59.4% were straight shaped and orientated backward respectively, in all agro-ecological zones. Faecal and blood samples were collected to assess the prevalence of GIN and genetic diversity of goats. The highest prevalence and abundance GIN parasites were Haemonchus contortus (nematode = 357.42) followed by Fasciola hapatica (trematode = 163) and Moniezia (cestodes = 121.50). The patterns of GIN prevalence varied (P < 0.05) across agro-ecological zones and seasons. Prevalence of Moniezia nematode varied (P < 0.05) amongst goat sexes, whilst prevalence of other GIN’s did not vary (P>0.05). For genetic variation in GIN resistance, goats were genotyped at 15 microsatellite markers recommended by the International Society of Animal Genetics. Expected heterozygosity (HE) ranged from 0.69 in arid zone goat population to 0.76 in sub-humid zone goat population, while the observed heterozygosity (HO) ranged from 0.53 in arid zone goat population to 0.60 in sub-humid zone goat population. Mean number of alleles (MNA) per population ranged from 6.13 to 7.40. Gene differentiation (FST) among populations was low (3.6%). The results revealed that genetic relationships between populations do not reflect their geographical proximity as revealed by the Nei’s genetic distance results. Low heterozygosity resulted in reducing some fitness traits for GIN parasite resistance. Inbreed goats showed low internal parasite resistance across all agro-ecological zones.