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Régulation de la division asymétrique chez C. elegansRabilotta, Alexia 07 1900 (has links)
No description available.
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The metabolic sequelae of oesophago-gastric resectionRoberts, Geoffrey Peter January 2019 (has links)
Bypass or resection of the stomach and oesophagus, has long been recognised to result in profound changes in the handling of ingested nutrients. This results in significant morbidity after radical surgery for oesophago-gastric cancer, in particular post-prandial hypoglycaemia, altered appetite, early satiety and noxious post-prandial symptoms. By profiling and challenging the gut hormone axis in healthy volunteers and patients who had undergone total or subtotal gastrectomy, or oesophagectomy, this thesis explores the possible causative mechanisms for the challenges faced by this patient population. In the surgical groups, an oral glucose tolerance test (OGTT) resulted in enhanced secretion of satiety and incretin gut hormones (GLP-1, GIP, PYY) and insulin, followed by hypoglycaemia in a cohort of patients. Continuous glucose monitoring of gastrectomy participants over two weeks of normal lifestyle identified an increased incidence of day and night time hypoglycaemia. RNAseq and mass spectrometry based peptidomics of human and murine enteroendocrine cells in the pre- and post-operative populations revealed no significant change in the underlying cellular pathways for nutrient sensing and gut hormone secretion, indicating that the altered hormone secretion is primarily driven by accelerated nutrient transit, rather than adaptive changes in the gut. Finally, specific blockade of the GLP-1 receptor in post-gastrectomy patients using Exendin 9-39 normalised insulin secretion and prevented reactive hypoglycaemia after an OGTT. In conclusion, profound changes in gut hormone secretion as a result of enhanced nutrient transit after foregut surgery likely underlie the early and late post-prandial symptoms seen in this group, and therapies specifically targeting the gut hormone axis, and GLP-1 in particular, could be the first targeted treatments for post-gastrectomy syndromes.
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ETUDES PHYSICO-CHIMIQUES DU GLUCAGON-LIKE PEPTIDE ET DE SON RECEPTEUR. OPTIQUE D'UNE NOUVELLE THERAPEUTIQUE POUR LE DIABETE DE TYPE IISarrauste de Menthière, Cyril 05 November 1999 (has links) (PDF)
Dans la perspective de trouver de nouvelles thérapies dans le traitement du diabète de type II, non insulino-dépendant, le Glucagon-Like Peptide-1 (GLP-1) constitue un excellent candidat. Si son mécanisme d'action est bien connu, il reste toutefois à résoudre de grands problèmes fondamentaux, avant de le substituer aux molécules utilisées pour une telle pathologie. En particulier, la compréhension de la liaison du GLP-1 à son récepteur demeure un point crucial. Une meilleure connaissance des structures du ligand et du récepteur sont nécessaires. De plus, ce peptide ne peut être utilisé dans sa forme native, dû à une inactivation rapide par les protéases.<br /><br />Pour essayer d'augmenter la stabilité du peptide, et en tenant compte des positions clés définies dans la littérature, plusieurs analogues du GLP-1-(7-37) sont conçus, et synthétisés. Ils possèdent principalement des pharmacomodulations au niveau de la partie N-terminale. Des substitutions sont également réalisées dans la partie centrale du peptide, permettant de vérifier certaines hypothèses concernant sa conformation. Considérant les résultats de liaison et d'efficacité in vitro, certains analogues sont sélectionnés pour des études in vivo d'activité et de stabilité métabolique. Le [a8,desR36]GLP-1-(7-37) se distingue des autres tant par sa grande stabilité que son efficacité, supérieure à la molécule native. Ce composé est en phase de développement pré-clinique.<br /><br />Parallèlement, la conformation de chaque analogue est étudiée (CD, IR) et ainsi, confrontée aux résultats in vitro, il est possible de proposer une conformation bioactive.<br /><br />Enfin, pour appréhender plus en avant les mécanismes de liaison du peptide avec son récepteur spécifique, la modélisation moléculaire du récepteur fait ressortir quelques hypothèses quant à la localisation probable de l'interaction hormone-récepteur. Des analyses biophysiques et la synthèse de fragments du récepteur, ont permis d'étayer de telles hypothèses.
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Benefícios Precoces da Cirurgia do Bypass Gástrico em Y de Roux: Implicações do GLP-1 e Adiponectina na Melhora do Perfil Metabólico de Pacientes com Diabetes Mellitus tipo 2 / Early benefits from Roux-en-Y gastric bypass surgery: implications of GLP-1 and adiponectin in the improvement of metabolic profile in the patients with type 2 diabetes mellitusUmeda, Luciana Mela [UNIFESP] 29 June 2011 (has links) (PDF)
Made available in DSpace on 2015-07-22T20:49:39Z (GMT). No. of bitstreams: 0
Previous issue date: 2011-06-29 / TEDE / BV UNIFESP: Teses e dissertações
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Efficacy of Bydureon in Adults with Type 2 DiabetesFetter, Katie L. 01 January 2014 (has links)
Type 2 diabetes is still rapidly on the rise today, affecting 10.5% of individuals in the United States between the ages 45 to 64 and 18.4% of those between the ages of 65 to 74. In the past two decades, type 2 diabetes has doubled in all age groups. Many adults with type 2 diabetes experience difficulty managing their blood sugars, which can result in a range of further complications. One of the newest treatment options on the market today is a glucagon-like peptide-1 (GLP-1) receptor agonist, Bydureon. Similar to Byetta, Bydureon has a main ingredient of exenatide. It offers once a week dosing as opposed to twice-a-day, which may be more appealing to patients.
The purpose of this study was to examine the efficacy of a newly FDA released medication, Bydureon, once weekly dosage in adults with type 2 diabetes. A descriptive, comparative, retrospective study of 35 patients evaluated efficacy by examining Hgb A1C and body mass index in adults with type 2 diabetes at baseline and 3 months after Bydureon was prescribed. Data were collected by a chart review of records in a primary care practice.
Results demonstrated a statistically significant difference between baseline to 3 month means in both Hgb A1C (t (34)= -3.05, p=.0044) and BMI (t (34) = -2.86, p = .0072) for patients using Bydureon.
Health care providers need to individualize the patients’ plans of care to address multifactorial areas of their diabetes care and provide them with an opportunity to successfully meet their goals. Practitioners must be knowledgeable about the treatment options available, including the newer GLP-1 receptor agonist, Bydureon and its efficacy for adults with type 2 diabetes.
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Impaired cardiovascular responses to glucagon-like peptide 1 in metabolic syndrome and type 2 diabetes mellitusMoberly, Steven Paul 30 January 2013 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Recent advancements in the management of systemic glucose regulation in obesity/T2DM include drug therapies designed to utilize components of the incretin system specifically related to glucagon-like peptide 1 (GLP-1). More recently, GLP-1 has been investigated for potential cardioprotective effects. Several investigations have revealed that acute/sub-acute intravenous administration of GLP-1 significantly reduces myocardial infarct size following ischemia/reperfusion injury and improves cardiac contractile function in the settings of coronary artery disease, myocardial ischemia/reperfusion injury, and heart failure. Despite an abundance of data indicating that intravenous infusion of GLP-1 is cardioprotective, information has been lacking on the cardiac effects of iv GLP-1 in the MetS or T2DM population. Some important questions this study aimed to address are 1) what are the direct, dose-dependent cardiac effects of GLP-1 in-vivo 2) are the cardiac effects influenced by cardiac demand (MVO2) and/or ischemia, 3) does GLP-1 effect myocardial blood flow, glucose uptake or total oxidative metabolism in human subjects, and 4) are the cardiac effects of GLP-1 treatment impaired in the settings of obesity/MetS and T2DM. Initial studies conducted in canines demonstrated that GLP-1 had no direct effect on
coronary blood flow in-vivo or vasomotor tone in-vitro, but preferentially increased myocardial glucose uptake in ischemic myocardium independent of effects on cardiac contractile function or coronary blood flow. Parallel translational studies conducted in the humans and Ossabaw swine demonstrate that iv GLP-1 significantly increases myocardial glucose uptake at rest and in response to increases in cardiac demand (MVO2) in lean subjects, but not in the settings of obesity/MetS and T2DM. Further investigation in isolated cardiac tissue from lean and obese/MetS swine indicate that this impairment in GLP-1 responsiveness is related to attenuated activation of p38-MAPK, independent of alterations in GLP-1 receptor expression or PKA-dependent signaling. Our results indicate that the affects of GLP-1 to reduce cardiac damage and increase left ventricular performance may be impaired by obesity/MetS and T2DM.
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[pt] AVALIAÇÃO METROLÓGICA EM OPERAÇÕES DE TRANSFERÊNCIAS DE CUSTÓDIA DE GLP / [en] METROLOGICAL EVALUATION IN LPG CUSTODY TRANSFER OPERATIONSPEDRO LINCOLN DE SOUZA FILHO 10 January 2022 (has links)
[pt] Esta dissertação visa a aplicar uma metodologia para avaliar as diferenças máximas permissíveis nas operações de transferência de custódia de GLP para cada operação em particular, utilizando testes de hipóteses baseados na incerteza de medição, em contraponto à utilização de valores pré-estabelecidos em normas e regulamentos técnicos metrológicos. Tais documentos propõem um valor único de incerteza máximas nas medições de transferência de custódia, sem estabelecer diferenças máximas permissíveis nas operações entre dois sistemas, cabendo aos fornecedores e clientes negociar este parâmetro, o que
frequentemente causa disputas. Os resultados mostraram que, em um sistema isolado, ao contrário de outros métodos, as condições ambientais não influenciam o método de medição de massa e sua incerteza. Nenhuma diferença máxima permissível de massa transferida de GLP entre caminhões-tanque e estações de medição excede 1,0 porcento; em contraste, quando uma esfera de armazenamento é parte de um dos sistemas de medição, este parâmetro depende completamente das condições operacionais e definitivamente um valor único não deve ser considerado. / [en] This dissertation aims to apply a methodology to assess the maximum allowable differences in LPG custody transfer operations for each particular operation, using hypothesis tests based on measurement uncertainty, as opposed to using pre-established values in metrological standards and technical regulations.
Such documents propose a single value for maximum uncertainty in custody transfer measurements, without establishing maximum permissible differences in operations between two systems, leaving it up to suppliers and customers to negotiate this parameter, which often causes disputes. The results showed that in an isolated system, unlike other methods, environmental conditions do not influence the mass measurement method and its uncertainty. No maximum permissible difference of transferred mass of LPG between tank trucks and measuring stations exceeds 1.0 percent; in contrast, when a storage sphere is part of one of the measuring systems, this parameter completely depends on the operating conditions and definitely a single value should not be considered.
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