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.

ABSTRACT Background Oesophageal cancer has a high mortality; it is the 6th most common cause of death due to cancer worldwide. Of the common subtypes of oesophageal cancer, it is the adenocarcinomas that have been rising rapidly in incidence throughout the western world. The incidence of adenocarcinomas now exceeds the previously common squamous cell carcinoma. These recent changes in the incidence patterns of oesophageal cancer suggests that the environmental risk factors associated with these subtypes differ, and that changes in the prevalence of these exposures over time are the most likely explanation for the observed shifts in the incidence. However, due to its low incidence until a few decades ago, the adenocarcinoma subtype has been less studied compared to squamous cell carcinoma, and the environmental factors associated with this cancer have not been so clearly defined. Smoking and alcohol have been the strongest environmental risk factors reported for oesophageal squamous cell carcinoma (OSCC) whereas for oesophageal adenocarcinoma (OAC), the effect of smoking appears to be weaker, and the evidence for an effect of alcohol is scant and inconsistent. However, epidemiologic studies consistently identify people with frequent symptoms of gastro-oesophageal reflux (GOR) as having the highest risk of OAC, but the effect of GOR on OSCC has been negligible. Furthermore, it has been argued that adenocarcinoma occurring at the gastro-oesophageal junction (GOJAC) may have different aetiology again. Together, these reports suggest the three subtypes of oesophageal cancers (OAC, GOJAC and OSCC) may arise through different mechanisms with different strengths in the impact of risk factors. This thesis investigated the independent associations of smoking, alcohol and gastro-oesophageal reflux on cancers of the oesophagus by considering the possibility of variation in the risks due to differences in the dose effect patterns of various measures such as smoking, alcohol and GOR. Method Data from a population-based case-control study of oesophageal and ovarian cancers in Australia were used. Study participants comprised histologically confirmed cases of OSCC (n=308), OAC (n=367) and GOJAC (n=426) who were frequency matched to 1580 controls from the general population. Exposure history for both cases and controls were derived from health and lifestyle questionnaires. Unconditional multivariate logistic regression was used to calculate the odds ratios and 95% confidence intervals for the risk factors analysed. In addition, generalised additive model with a logit link was also used to explore and present the non-linearity in the dose effect pattern for continuous exposures adjusting for other confounding factors. The effects of two exposures combined on these cancers were assessed by obtaining synergy index. Results Smokers were at significantly higher risk of all three subtypes of oesophageal cancer with the risk greatest for OSCC. The effect of smoking was greater for adenocarcinoma occurring at the gastro-oesophageal junction compared to that of the oesophagus. Of the various measures of smoking, duration was significantly associated with all three subtypes of cancer whereas intensity was associated with only OSCC and GOJAC and the dose effect was non-linear. Time since quitting was associated with a steady decline in risk of all three cancers emphasising the health benefits of quitting among smokers. Alcohol was not associated with OAC or GOJAC but was significantly associated with OSCC among those drinking in excess of 170g/week. The association between alcohol and OSCC was modified by smoking; the association with alcohol was significantly greater among current smokers with effect. Low to moderate wine consumption was associated with significant risk reduction for all three cancers compared to non-drinkers. Increased frequency of GOR symptoms was associated with increased risks of OAC and GOJAC, although the risk of OSCC was constrained to frequent GOR symptoms only. The effect of GOR symptoms were exacerbated by smoking whereas it was weakened by regular NSAID use. Lastly, the sensitivity analysis that assessed the effect of non-participation among controls in the estimated effect of smoking and BMI (the two risk factors most likely to be affected by non-participation) showed a slight overestimation of effect of smoking assuming higher exposure rate among non-participants but not BMI while the effect remained strong and statistically significant. Conclusion Smoking, alcohol and GOR symptoms were the environmental factors strongly associated with all subtypes of oesophageal cancers. However, the dose effect patterns of these exposures varied by cancer subtypes. Smoking and alcohol were the larger contributing factors for OSCC whereas smoking and GOR symptoms had greater impact on OAC and GOJAC. Low to moderate wine consumption and regular NSAID use reduced the risk of all three subtypes significantly. While selection bias may have led to mildly inflated risks for smoking, the effects persisted even when modelled under extreme scenarios of biased participation amongst controls, and there was no evidence that selection bias materially affected the other associations.

ABSTRACT Background Oesophageal cancer has a high mortality; it is the 6th most common cause of death due to cancer worldwide. Of the common subtypes of oesophageal cancer, it is the adenocarcinomas that have been rising rapidly in incidence throughout the western world. The incidence of adenocarcinomas now exceeds the previously common squamous cell carcinoma. These recent changes in the incidence patterns of oesophageal cancer suggests that the environmental risk factors associated with these subtypes differ, and that changes in the prevalence of these exposures over time are the most likely explanation for the observed shifts in the incidence. However, due to its low incidence until a few decades ago, the adenocarcinoma subtype has been less studied compared to squamous cell carcinoma, and the environmental factors associated with this cancer have not been so clearly defined. Smoking and alcohol have been the strongest environmental risk factors reported for oesophageal squamous cell carcinoma (OSCC) whereas for oesophageal adenocarcinoma (OAC), the effect of smoking appears to be weaker, and the evidence for an effect of alcohol is scant and inconsistent. However, epidemiologic studies consistently identify people with frequent symptoms of gastro-oesophageal reflux (GOR) as having the highest risk of OAC, but the effect of GOR on OSCC has been negligible. Furthermore, it has been argued that adenocarcinoma occurring at the gastro-oesophageal junction (GOJAC) may have different aetiology again. Together, these reports suggest the three subtypes of oesophageal cancers (OAC, GOJAC and OSCC) may arise through different mechanisms with different strengths in the impact of risk factors. This thesis investigated the independent associations of smoking, alcohol and gastro-oesophageal reflux on cancers of the oesophagus by considering the possibility of variation in the risks due to differences in the dose effect patterns of various measures such as smoking, alcohol and GOR. Method Data from a population-based case-control study of oesophageal and ovarian cancers in Australia were used. Study participants comprised histologically confirmed cases of OSCC (n=308), OAC (n=367) and GOJAC (n=426) who were frequency matched to 1580 controls from the general population. Exposure history for both cases and controls were derived from health and lifestyle questionnaires. Unconditional multivariate logistic regression was used to calculate the odds ratios and 95% confidence intervals for the risk factors analysed. In addition, generalised additive model with a logit link was also used to explore and present the non-linearity in the dose effect pattern for continuous exposures adjusting for other confounding factors. The effects of two exposures combined on these cancers were assessed by obtaining synergy index. Results Smokers were at significantly higher risk of all three subtypes of oesophageal cancer with the risk greatest for OSCC. The effect of smoking was greater for adenocarcinoma occurring at the gastro-oesophageal junction compared to that of the oesophagus. Of the various measures of smoking, duration was significantly associated with all three subtypes of cancer whereas intensity was associated with only OSCC and GOJAC and the dose effect was non-linear. Time since quitting was associated with a steady decline in risk of all three cancers emphasising the health benefits of quitting among smokers. Alcohol was not associated with OAC or GOJAC but was significantly associated with OSCC among those drinking in excess of 170g/week. The association between alcohol and OSCC was modified by smoking; the association with alcohol was significantly greater among current smokers with effect. Low to moderate wine consumption was associated with significant risk reduction for all three cancers compared to non-drinkers. Increased frequency of GOR symptoms was associated with increased risks of OAC and GOJAC, although the risk of OSCC was constrained to frequent GOR symptoms only. The effect of GOR symptoms were exacerbated by smoking whereas it was weakened by regular NSAID use. Lastly, the sensitivity analysis that assessed the effect of non-participation among controls in the estimated effect of smoking and BMI (the two risk factors most likely to be affected by non-participation) showed a slight overestimation of effect of smoking assuming higher exposure rate among non-participants but not BMI while the effect remained strong and statistically significant. Conclusion Smoking, alcohol and GOR symptoms were the environmental factors strongly associated with all subtypes of oesophageal cancers. However, the dose effect patterns of these exposures varied by cancer subtypes. Smoking and alcohol were the larger contributing factors for OSCC whereas smoking and GOR symptoms had greater impact on OAC and GOJAC. Low to moderate wine consumption and regular NSAID use reduced the risk of all three subtypes significantly. While selection bias may have led to mildly inflated risks for smoking, the effects persisted even when modelled under extreme scenarios of biased participation amongst controls, and there was no evidence that selection bias materially affected the other associations.

ABSTRACT Background Oesophageal cancer has a high mortality; it is the 6th most common cause of death due to cancer worldwide. Of the common subtypes of oesophageal cancer, it is the adenocarcinomas that have been rising rapidly in incidence throughout the western world. The incidence of adenocarcinomas now exceeds the previously common squamous cell carcinoma. These recent changes in the incidence patterns of oesophageal cancer suggests that the environmental risk factors associated with these subtypes differ, and that changes in the prevalence of these exposures over time are the most likely explanation for the observed shifts in the incidence. However, due to its low incidence until a few decades ago, the adenocarcinoma subtype has been less studied compared to squamous cell carcinoma, and the environmental factors associated with this cancer have not been so clearly defined. Smoking and alcohol have been the strongest environmental risk factors reported for oesophageal squamous cell carcinoma (OSCC) whereas for oesophageal adenocarcinoma (OAC), the effect of smoking appears to be weaker, and the evidence for an effect of alcohol is scant and inconsistent. However, epidemiologic studies consistently identify people with frequent symptoms of gastro-oesophageal reflux (GOR) as having the highest risk of OAC, but the effect of GOR on OSCC has been negligible. Furthermore, it has been argued that adenocarcinoma occurring at the gastro-oesophageal junction (GOJAC) may have different aetiology again. Together, these reports suggest the three subtypes of oesophageal cancers (OAC, GOJAC and OSCC) may arise through different mechanisms with different strengths in the impact of risk factors. This thesis investigated the independent associations of smoking, alcohol and gastro-oesophageal reflux on cancers of the oesophagus by considering the possibility of variation in the risks due to differences in the dose effect patterns of various measures such as smoking, alcohol and GOR. Method Data from a population-based case-control study of oesophageal and ovarian cancers in Australia were used. Study participants comprised histologically confirmed cases of OSCC (n=308), OAC (n=367) and GOJAC (n=426) who were frequency matched to 1580 controls from the general population. Exposure history for both cases and controls were derived from health and lifestyle questionnaires. Unconditional multivariate logistic regression was used to calculate the odds ratios and 95% confidence intervals for the risk factors analysed. In addition, generalised additive model with a logit link was also used to explore and present the non-linearity in the dose effect pattern for continuous exposures adjusting for other confounding factors. The effects of two exposures combined on these cancers were assessed by obtaining synergy index. Results Smokers were at significantly higher risk of all three subtypes of oesophageal cancer with the risk greatest for OSCC. The effect of smoking was greater for adenocarcinoma occurring at the gastro-oesophageal junction compared to that of the oesophagus. Of the various measures of smoking, duration was significantly associated with all three subtypes of cancer whereas intensity was associated with only OSCC and GOJAC and the dose effect was non-linear. Time since quitting was associated with a steady decline in risk of all three cancers emphasising the health benefits of quitting among smokers. Alcohol was not associated with OAC or GOJAC but was significantly associated with OSCC among those drinking in excess of 170g/week. The association between alcohol and OSCC was modified by smoking; the association with alcohol was significantly greater among current smokers with effect. Low to moderate wine consumption was associated with significant risk reduction for all three cancers compared to non-drinkers. Increased frequency of GOR symptoms was associated with increased risks of OAC and GOJAC, although the risk of OSCC was constrained to frequent GOR symptoms only. The effect of GOR symptoms were exacerbated by smoking whereas it was weakened by regular NSAID use. Lastly, the sensitivity analysis that assessed the effect of non-participation among controls in the estimated effect of smoking and BMI (the two risk factors most likely to be affected by non-participation) showed a slight overestimation of effect of smoking assuming higher exposure rate among non-participants but not BMI while the effect remained strong and statistically significant. Conclusion Smoking, alcohol and GOR symptoms were the environmental factors strongly associated with all subtypes of oesophageal cancers. However, the dose effect patterns of these exposures varied by cancer subtypes. Smoking and alcohol were the larger contributing factors for OSCC whereas smoking and GOR symptoms had greater impact on OAC and GOJAC. Low to moderate wine consumption and regular NSAID use reduced the risk of all three subtypes significantly. While selection bias may have led to mildly inflated risks for smoking, the effects persisted even when modelled under extreme scenarios of biased participation amongst controls, and there was no evidence that selection bias materially affected the other associations.

Orientador: Chung Man Chin / Banca: Leoberto Costa Tavares / Banca: Agnaldo Bruno Chies / Banca: Maria do Carmo Longo / Banca: Veni Maria Andres Felli / Resumo: A inflamação é uma reação de defesa e reparo fisiológico, importante em resposta a agressões físicas, químicas ou biológicas ao organismo, que geram o aparecimento dos quatro sinais cardinais dor, edema, calor, rubor, incluindo, muitas vezes a perda de função do tecido ou órgão. O processo inflamatório agudo é imediato e inespecífico contra o agente agressor, podendo evoluir para crônico, caso haja a permanência do agente agressivo e é caracterizado pelo aumento de celularidade e outros elementos teciduais. Várias substâncias estão envolvidas no processo inflamatório, como a prostaglandinas, histamina, serotonina e citocinas pró-inflamatórias como IL-1b, 1L-6, IL-8, TNF-a, NF-kB. Estima-se que exista na terapêutica, mais de 50 antiinflamatórios não esteróides (AINEs) diferentes, mas nenhum deles totalmente destituído de efeitos tóxicos, como a gastrotoxicidade, mesmo os compostos mais novos, seletivos para receptores COX2, como o celecoxibe. Por este motivo nenhum AINEs é recomendado para utilização em processos inflamatórios crônicos. Neste sentido, Vizioli (2006) e Castro (2008), planejaram pró-fármacos taurínicos e híbridos ftalimídicos, respectivamente, obtendo resultados promissores como antiinflamatórios potenciais destituídos de gastrotoxicidade. O presente trabalho visa realizar os testes pré-clinicos de atividade antiinflamatória aguda e crônica. Os resultados demostraram que que todos os derivados testados não apresentam gastrotoxicidade em relação ao padrão AINE testado, sem alteração significativa da resposta inflamatória aguda, com exceção do derivado de ibuprofeno N-(1,3-dioxo-1,3-diidro-2H-isoindol-2-il)-2-(4-isobutilfenil) propanamida, que demonstrou atividade inferior. Em estudo de atividade inflamatória crônica... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Inflammation is a defense and repair physiologic reaction important in response to an physical, chemical or biological aggression of the body, providing the appearance of the four cardinal signs of pain, swelling, heat, redness, including often the loss of function of the tissue or organs. The acute inflammatory process is immediate and nonspecific against the aggressive agent and it is characterized by increased cellular and other tissue elements. Series of substances are involved in the inflammatory process such as prostaglandins, histamine, serotonin and pro-inflammatory cytokines such as 1L-6, IL-8, a-TNF, NF- kB. It is estimated that exists more than 50 different non steroidal anti-inflammatory drugs (NSAIDs) drugs in the market, but none of them are wholly without side effects such as gastro toxicity, even the newer compounds, selective to COX2 receptors, as the celecoxib. For this reason none of NSAIDs is recommended for use in chronic inflammatory diseases. In this sense, Vizioli (2006) and Castro (2008), planned new taurine prodrugs and phtalimide hybride NSAIDs, respectively, showing promising results as anti-inflammatory without toxicity. This work aims to accomplish pre-clinical assay by acute and chronic models of inflammation. The results showed that all derivatives tested have no gastro toxicity when compared with the NSAIDs standard. No significant inflammatory response was observed with the exception toibuprofen derivative N-(1,3-dioxo-1,3-diidro-2H-isoindol-2-il)-2-(4-isobutilfenil) propanamide, which showed less activity. In the chronic inflammatory study activity all compounds phthalimide and taurine showed increase of activity compared to standard NSAIDs with decrease of the mortality and exclusion of the clinical signals such as bleeding, weight loss, and increased defecation rate... (Complete abstract click electronic access below) / Doutor

Cápsulas resistentes ao trato gastrintestinal são freqüentemente usadas com diversos propósitos. Estas cápsulas promovem eficácia farmacológica e farmacocinética de substâncias que são instáveis, ou irritantes para a mucosa gástrica. O diclofenaco de sódio é um antiinflamatório não-esteróide, que, por ser muito utilizado, despertou o interesse do setor magistral para sua manipulação. Porém, o fármaco é irritante para a mucosa gástrica, havendo necessidade de se empregar substâncias capazes de proteger o meio gástrico da ação do medicamento e uma alternativa para o setor magistral é a manipulação de cápsulas gastro-resistentes. Estas cápsulas devem resistir, sem alteração, à ação do suco gástrico, mas desagregar-se rapidamente no suco intestinal. O objetivo deste trabalho foi preparar cápsulas na concentração de 50 mg/cápsula de diclofenaco de sódio formiladas ou revestidas com acetoftalato de celulose ou com Eudragit L100 na máquina de revestimento entérico “Enteric Coating Machine” PCCA ou manualmente. Foram analisados os resultados considerando o perfil de dissolução das formulações. Observou-se que as cápsulas revestidas na máquina com Eudragit L100 e com acetoftalato em acetona revestidas na máquina e manualmente mostraram bons resultados quanto à dissolução, porém, não apresentaram boa aparência no caso das cápsulas de cor vermelha. Quanto às cápsulas revestidas com formol, estas apresentam boa aparência, mas não deram bons resultados no teste de dissolução.

Cápsulas resistentes ao trato gastrintestinal são freqüentemente usadas com diversos propósitos. Estas cápsulas promovem eficácia farmacológica e farmacocinética de substâncias que são instáveis, ou irritantes para a mucosa gástrica. O diclofenaco de sódio é um antiinflamatório não-esteróide, que, por ser muito utilizado, despertou o interesse do setor magistral para sua manipulação. Porém, o fármaco é irritante para a mucosa gástrica, havendo necessidade de se empregar substâncias capazes de proteger o meio gástrico da ação do medicamento e uma alternativa para o setor magistral é a manipulação de cápsulas gastro-resistentes. Estas cápsulas devem resistir, sem alteração, à ação do suco gástrico, mas desagregar-se rapidamente no suco intestinal. O objetivo deste trabalho foi preparar cápsulas na concentração de 50 mg/cápsula de diclofenaco de sódio formiladas ou revestidas com acetoftalato de celulose ou com Eudragit L100 na máquina de revestimento entérico “Enteric Coating Machine” PCCA ou manualmente. Foram analisados os resultados considerando o perfil de dissolução das formulações. Observou-se que as cápsulas revestidas na máquina com Eudragit L100 e com acetoftalato em acetona revestidas na máquina e manualmente mostraram bons resultados quanto à dissolução, porém, não apresentaram boa aparência no caso das cápsulas de cor vermelha. Quanto às cápsulas revestidas com formol, estas apresentam boa aparência, mas não deram bons resultados no teste de dissolução.

En 2016, environ 53 070 patients ont reçu un diagnostic d'adénocarcinome canalaire pancréatique (PDA) aux États-Unis et la plupart d'entre eux mourront de leur maladie dans les 5 ans. Le registre belge du cancer rapporte une incidence estimée à 1200 nouveaux cas par an. La survie globale à 5 ans pour toutes stades confondus a marginalement augmenté au cours des 50 dernières années, passant de 2 à 6%, malgré l'imagerie, les soins périopératoires et l'amélioration des techniques chirurgicales.La chirurgie reste la seule chance de guérison, cependant, seulement 10-15% des patients nouvellement diagnostiqués sont jugés éligibles pour une chirurgie. Même s'il existe peu d'autres modalités de traitement efficaces qui puissent considérablement prolonger la survie globale, la plupart des patients finiront par mourir de métastases au foie, au poumon et / ou au péritoine, les sites de propagation les plus courants. Les patients, les cliniciens et les chercheurs restent frustrés par le manqué d’outils thérapeutiques et des nouvelles stratégies sont nécessaires pour comprendre et mieux prendre en charge cette maladie.Le terme «cancer» engendre un sentiment de peur et colère, en particulier quand on est confronté au diagnostic dévastateur de cancer du pancréas. En plus, une réaction commune est de personnifier le cancer comme une entité maléfique qui doit être combattue pour sauver la vie du patient. Les armes pour cette bataille comprennent le scalpel d'un chirurgien, la chimiothérapie, la radiothérapie, les thérapies ciblées, les immunothérapies, les approches holistiques et la foi religieuse. Mais nous avons trop souvent oublié ou sous-estimé la contribution de la recherche translationnelle pour la médecine de précision, pour mieux adapter les thérapies et éviter les toxicités inutiles.Dans un sens biologique, qu'est-ce qu'un cancer du pancréas ou un cancer? Le cancer est une maladie génétique, soumise à un phénomène évolutif avec ses propres règles, contraintes et caractéristiques prévisibles qui mènent finalement à un phénotype unique.La stratégie "one size fits all" dans la PDA a souvent échoué dans les essais de nouveaux médicaments dans une population non sélectionnée.Cette thèse est une contribution modeste et authentique à une approche plus personnalisée du PDA, de l'acquisition tissulaire, à l'analyse de biomarqueurs tissulaires, à une analyse moléculaire plus profonde afin de mieux comprendre cette maladie mortelle et de proposer l'intégration de biomarqueurs dans le developpement d’etudes cliniques guides par les analyses moléculaires. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Cápsulas resistentes ao trato gastrintestinal são freqüentemente usadas com diversos propósitos. Estas cápsulas promovem eficácia farmacológica e farmacocinética de substâncias que são instáveis, ou irritantes para a mucosa gástrica. O diclofenaco de sódio é um antiinflamatório não-esteróide, que, por ser muito utilizado, despertou o interesse do setor magistral para sua manipulação. Porém, o fármaco é irritante para a mucosa gástrica, havendo necessidade de se empregar substâncias capazes de proteger o meio gástrico da ação do medicamento e uma alternativa para o setor magistral é a manipulação de cápsulas gastro-resistentes. Estas cápsulas devem resistir, sem alteração, à ação do suco gástrico, mas desagregar-se rapidamente no suco intestinal. O objetivo deste trabalho foi preparar cápsulas na concentração de 50 mg/cápsula de diclofenaco de sódio formiladas ou revestidas com acetoftalato de celulose ou com Eudragit L100 na máquina de revestimento entérico “Enteric Coating Machine” PCCA ou manualmente. Foram analisados os resultados considerando o perfil de dissolução das formulações. Observou-se que as cápsulas revestidas na máquina com Eudragit L100 e com acetoftalato em acetona revestidas na máquina e manualmente mostraram bons resultados quanto à dissolução, porém, não apresentaram boa aparência no caso das cápsulas de cor vermelha. Quanto às cápsulas revestidas com formol, estas apresentam boa aparência, mas não deram bons resultados no teste de dissolução.

L’endoscopie flexible a considérablement évolué au cours des cinquante dernières années. D’une procédure purement diagnostique, elle est aujourd’hui principalement thérapeutique. Des procédures telles que dilatation, implantation de prothèse et polypectomie sont pratiquées quotidiennement dans des centres qualifiés.Depuis toujours l’apposition tissulaire est pratiquée par les chirurgiens pour réaliser des anastomoses et des sutures. L’apposition de séreuse à séreuse, créant un attachement permanent par la cicatrisation, ne s’est développée que récemment en endoscopie. Pour réaliser cela, de nouveaux outils devaient être créés. L’idée principale pour permettre d’apposer et de suturer des tissus est d’obtenir un système de triangulation permettant de travailler perpendiculairement à l’axe de l’endoscope.En collaboration avec les ingénieurs de la faculté polytechnique de notre Université, un nouveau système de triangulation a été créé. Au début complexe et manipulé par un système robotique, il a ensuite été simplifié pour devenir mécanique et rigide.Cette plateforme pouvant être assemblée à l’intérieur du corps permet la réalisation de sutures endoluminales, sans équivalent actuel parmi les dispositifs médicaux disponibles. Cela nous a permis de mener des études scientifiques pour tester la validité, la sécurité et enfin l’efficacité de ce dispositif, ainsi que de concevoir et d’améliorer la technique dans une indication bariatrique, et de rechercher de nouvelles indications.La première partie de notre travail a révélé la performance de la réduction gastrique dans la prise en charge des patients obèses. La procédure a initialement été conçue et testée sur des animaux, puis une première étude de sécurité chez l’homme a été menée. Cette étude a mis en évidence la sécurité de la technique mais a également fourni des résultats préliminaires en termes d’efficacité. Une deuxième étude multicentrique d’efficacité a ensuite été menée sur 51 patients. Les résultats de cette étude ont été positifs en termes de perte de poids et de sécurité de la technique. Ensuite, pour évaluer l’efficacité intrinsèque de la procédure, une étude randomisée a été menée. Actuellement tous les patients ont été inclus. Le suivi à 1 an n’est pas encore disponible mais les résultats préliminaires à 6 mois sont discutés.Ayant ce nouveau dispositif à notre disposition, nous nous sommes intéressés à d’autres indications. La première concernait le traitement des diverticules œsophagiens, une maladie bénigne et difficile à traiter, que nous avons abordée initialement avec un traitement utilisant des aimants pour l’apposition des tissus. Cependant le système de sutures, initialement développé, a été modifié et utilisé avec succès dans cette indication. Parmi les autres indications explorées figurent le syndrome de l’anse afférente et la reprise de poids post Bypass gastrique. Ces études sont toujours en cours.La résection en paroi complète est une autre indication que nous avons évaluée. Dans cette indication particulière, nous avons effectué une première étude de sécurité et de faisabilité animale, qui nous a permis, via des ajustements de matériel, de démarrer une étude chez l’homme. Le premier patient traité avec succès ayant déjà été rapporté.Nous évaluons actuellement d’autres indications telles que le traitement des comorbidités associées à l’obésité (Diabète de type 2 et NASH) ou la prise en charge du reflux gastro-œsophagien.En résumé, ce travail rend compte des différentes études cliniques issues du développement, avec nos collègues ingénieurs, d’un nouveau dispositif médical. Il illustre les différentes étapes nécessaire pour établir la sécurité et l’efficacité d’une nouvelle procédure qui pourrait représenter un changement de paradigme dans la gestion de l’obésité, mais montre également comment un nouveau concept peut représenter un intérêt pour d’autres indications rares et nouvelles. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished