Yes / Medical technologies have the potential to improve quality and efficiency of healthcare. The design of clinical trials should consider participants' perspectives to optimise enrolment, engagement and satisfaction. This study aims to assess patients' perceptions of their involvement in medical device trials, to inform the designs of future medical technology implementation and evaluation. Four focus groups were undertaken with a total of 16 participants who had participated in a study testing hospital inpatient remote monitoring devices. Interviews were audio-recorded, transcribed verbatim and underwent thematic analysis. Four main themes emerged: patients' motivations for participating in medical device research; patients' perceptions of technology in medicine; patients' understanding of trial methodology; and patients' perceptions of the benefits of involvement in medical device trials. The appeal of new technology is a contributing factor to the decision to consent, although concerns remain regarding risks associated with technology in healthcare settings. Perceived benefits of participating in device trials include extra care, social benefits and comradery with other participants seen using the devices, although there is a perceived lack of confidence in using technology amongst older patients. Future device trials should prioritise information sharing with participants both before and after the trial. Verbal and written information alongside practical demonstrations can help to combat a lack of confidence with technology. Randomised trials and those with placebo- or sham-controlled arms should not be considered as barriers to participation. Study results should be disseminated to participants in lay format as soon as possible, subject to participant permission. / The patients in this study were participating in a randomised controlled trial funded by a Health Foundation Innovating for Improvement Award (Grant number: GIFTS 7643 CRM 2674). Candice Downey is in possession of a Doctoral Research Fellowship (DRF-2016-09- 037) supported by the National Institute for Health Research. DGJ received funding support through an NIHR Research Professorship. The research is supported by the NIHR infrastructure at Leeds.

-- Thèse fournie sans page de titre --Afin de mieux comprendre la physiopathologie des causes gastriques de malabsorption de la vitamine B12, nous nous sommes intéressés au déficit congénital en facteur intrinsèque, une maladie rare caractérisée par une diminution de la sécrétion de facteur intrinsèque (FI) fonctionnel dans le suc gastrique. Dans cette étude, nous rapportons cinq cas porteurs hétérozygotes du variant GIF c.290T>C (p.M97T) et deux cas porteurs hétérozygotes du variant GIF c.435_437delGAA (p.K145_N146delinsN). L'étude fonctionnelle des FI recombinants mutés produits par mutagenèse dirigée a mis en évidence une diminution de l'affinité du FI p.K145_N146delinsN pour la vitamine B12 n'expliquant toutefois pas totalement le phénotype observé chez les sujets. Par ailleurs, une association a été récemment décrite entre le polymorphisme rs601338, c.461 G>A du gène FUT2, codant pour une [alpha]1,2-fucosyltransférase, et les taux plasmatiques de vitamine B12. Afin de compléter notre étude, nous avons évalué l'influence du polymorphisme FUT2 c.461 G>A sur les taux de vitamine B12, de folates et d'homocystéine dans les populations Européennes et Africaines chez 1466 sujets. Notre étude démontre un effet du polymorphisme FUT2 c.461 G>A sur les taux plasmatiques de vitamine B12 et de folates indépendamment de l'âge, du sexe et de l'origine géographique. En conclusion, nos résultats démontrent que le gène du FI (GIF) n'est pas le seul gène impliqué dans la physiopathologie du déficit congénital en facteur intrinsèque. L'étude des malabsorptions d'origine gastrique de la vitamine B12 passe par une approche polygénique dans laquelle le gène FUT2 occupe une place importante / There are multiple causes of gastric vitamin B12 malabsorption. To get a better understanding of their physiopathology, we are interested in inherited gastric intrinsic factor (GIF) deficiency, a vitamin B12 absorption defect characterized by GIF impaired activity. In this study, we report five cases heterozygous carriers of the variant GIF c.290T>C (p.M97T) and two cases heterozygous carriers of the variant GIF c.435_437delGAA (p.K145_N146delinsN). The study of recombinant mutated GIF produced by site-directed mutagenesis evidenced a reduced affinity for vitamin B12 in the case of GIF p.K145_N146delinsN which does not explain fully the phenotypes observed in our subjects. Recently, an association was described between the FUT2 polymorphism rs601338, c.461 G>A, coding for a fucosyltransferase, and plasma levels of vitamin B12. To complete our study, we assessed the influence of FUT2 c.461 G>A polymorphism on vitamin B12, folate and homocysteine in European and African populations in 1466 subjects. Our study demonstrate a clear effect of FUT2 c.461 G>A polymorphism on both plasma levels of vitamin B12 and folate, regardless of age, gender, and geographic origin. In conclusion, our results demonstrate the GIF gene is not the only gene involved in the physiopathology of inherited GIF deficiency. It is necessary to study the gastric causes of vitamin B12 malabsorption through a polygenic approach, in which the FUT2 gene is an important element

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O carcinoma gÃstrico à a segunda causa de morte por cÃncer no mundo. No Cearà à o segundo mais freqÃente entre os homens e o terceiro entre as mulheres. Dos cÃnceres gÃstricos os adenocarcinomas representam em torno de 95%. A doenÃa tem sido associada a fatores genÃticos e ambientais sendo demonstrada Ãntima relaÃÃo com a infecÃÃo por Helicobacter pylori, principalmente associada à presenÃa do gene cagA e genÃtipos vacAs1m1. Entretanto, apesar dos mecanismos pelos quais a bactÃria promove a carcinogÃnese gÃstrica ainda nÃo estarem esclarecidos, uma das hipÃteses seria atravÃs da inativaÃÃo de supressores tumorais. O objetivo do presente trabalho foi verificar, em adenocarcinomas gÃstricos, se a presenÃa de H. pylori, e de seus genes cagA e vacA, està relacionada com a mutaÃÃo e/ou alteraÃÃo na expressÃo protÃica dos supressores tumorais p53 e p27. Neste estudo, 74 amostras de pacientes foram analisadas quanto à presenÃa de H. pylori, cagA+ e os genÃtipos de vacA, pela reaÃÃo em cadeia da polimerase (PCR). A anÃlise mutacional do gene p53 foi realizada por PCR-SSCP e a detecÃÃo da mutaÃÃo/superexpressÃo do p53 e expressÃo da proteÃna p27 pelo mÃtodo imunohistoquÃmico. A bactÃria foi detectada em 95% das amostras, das quais 63% eram cagA(+). Dentre os alelos de vacA, observou-se predomÃnio de s1 (74%) e m1 (82%), associados em 69% dos casos. Na anÃlise mutacional do p53 verificou-se que 72% dos casos exibiram alteraÃÃo no padrÃo de mobilidade eletroforÃtica, sendo esta associada significativamente à presenÃa do gene cagA. Por outro lado, apenas 29% dos casos apresentaram detecÃÃo pelo mÃtodo imunohistoquÃmico, nÃo sendo encontrada associaÃÃo com a H. pylori. A proteÃna p27 demonstrou acentuada reduÃÃo em sua expressÃo (detectada em apenas 19% dos casos), nÃo demonstrando atividade compensatÃria em relaÃÃo à proteÃna p53 mutada e sem associaÃÃo estatÃstica dos casos negativos com a presenÃa da H. pylori. Finalmente, os resultados sugerem que estes supressores simultaneamente inativados podem ser o ponto chave da desregulaÃÃo do ciclo celular que, associados a outros fatores, favoreÃam o desenvolvimento e progressÃo dos adenocarcinomas gÃstricos. Hà indÃcios de que a presenÃa bacteriana, e dos seus genes cagA(+) e vacA/s1m1, possam influenciar, de forma nÃo esclarecida, as alteraÃÃes moleculares ocorridas nos supressores tumorais p53 e p27. / Gastric carcinoma is the second cause of death by cancer in the world. On State of Ceara-Brazil is the second most frequent type of cancer in men and third in women. Adenocarcinomas account for approximately 95% of all malignant gastric neoplasms. It has been associated to genetic and environmental factors and a intimate relationship between the infection by the bacteria Helicobacter pylori and the gastric carcinoma have been related. The presence of the cagA gene and specific genotypes (s1m1) of the gene vacA have been detected in more pathogenic strains. Although the precise molecular mechanisms by which H. pylori could promote the process of gastric carcinogenesis are under investigation, one hypothesized mechanism involves the tumor supressor genes inactivation. The aim of the present study was to verify if the presence of Helicobacter pylori, cagA and vacA genes is related to mutations in the tumor supressor gene p53 and altered expression of p53 and p27 proteins in gastric adenocarcinomas. Seventy-four (74) samples were analyzed to detect the presence of H. pylori, cagA and genotypes of vacA by Polymerization Chain Reaction (PCR). The mutational analysis of p53 gene was performed by PCR-SSCP (Polymerization Chain Reaction for analysis of the Single-strand Conformation Polymorphism). Analysis of mutation or overexpression of p53 protein and p27 expression was detected by the immunohistochemical method. The bacteria was detected in 95% of the samples, 63% was cagA(+). Among the vacA allele it was observed prevalence of s1 (74%) and m1 (82%), associated in 69% of the cases. Mutation analysis of p53 demonstrated 72% of the cases with altered electrophoretic mobility; The alterations were significatively more frequent in the presence of the cagA gene. Immunohistochemical analysis detected only 29% of cases with the expression of p53 protein. The protein p27 showed accentuated reduction in its expression (detected in only 19% of the cases), it has not demonstrated compensatory activity in relation to the p53 altered protein, neither association to H. pylori presence. Finally, these data suggest that simultaneous inactivation of these tumor suppressors genes may be the key point of deregulation of the cellular cycle that, associated to the other factors, favor the development and progression of the gastric cancer. There is some evidence that the bacterial presence, cagA and vacA/s1m1 genes, may influence, in a not understood way, the alterations observed in the tumor suppressors p53 and p27.

Submitted by Natalia de Souza Gonçalves (natalia.goncalves@ufpe.br) on 2016-10-10T13:09:11Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) GALENO EGYDIO - COLACAO DE GRAU.pdf: 1509311 bytes, checksum: f4dc67e7a0e6a1a9159df433631ba569 (MD5) / Made available in DSpace on 2016-10-10T13:09:12Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) GALENO EGYDIO - COLACAO DE GRAU.pdf: 1509311 bytes, checksum: f4dc67e7a0e6a1a9159df433631ba569 (MD5) Previous issue date: 2014-02-19 / O uso de anel na derivação gástrica em Y de Roux (DGYR) está associado à intolerância alimentar pós-operatória, cujo tratamento clássico tem sido a remoção cirúrgica. Um novo método utilizando prótese plástica autoexpansível (PPAE) induz erosão intragástrica do anel, o qual é removido por via endoscópica de forma minimamente invasiva. Objetiva-se analisar a eficácia e a segurança dessa técnica de remoção de anel após DGYR. Estudo prospectivo longitudinal de série de 41 pacientes com intolerância alimentar associada à presença de anel, que foram, tratados por via endoscópica, entre 2007 e 2013. O grupo apresentava média de idade igual a 44,1 anos, IMC médio de 27,0 Kg/m², e vômitos foram os sintomas mais frequentes (n=37), com ocorrência diária em 46,3%. O sucesso terapêutico foi definido como a melhora dos sintomas após a remoção do anel. O implante de PPAE foi realizado sob anestesia geral e guiado por radioscopia, sendo utilizado endoscópio padrão. Os pacientes receberam alta após 24 horas com dieta líquida e inibidor de bomba de prótons (IBP), que foi prescrito durante o tempo médio de permanência da PPAE, que foi de 15,3 dias. A prótese promoveu erosão completa de anel em 24 (58,5%) pacientes e no grupo restante, a remoção em segundo estágio após 7 dias com pinça de corpo estranho. Houve três casos de migração da prótese com eliminação espontânea por via retal. O efeito adverso mais comum foi vômito (n=7). Não houve complicações graves, nem necessidade de remoção precoce da prótese. Após seguimento médio de 6 meses, não houve mudança significativa no IMC e 78% dos pacientes foram capazes de ingerir carne vermelha. A remoção do anel com uso de prótese endoscópica demonstrou ser um procedimento seguro e eficaz, com100% dos anéis sendo removidos com sucesso e 29,3% de ocorrência de eventos adversos leves (vômitos). Esta técnica é uma alternativa adequada na remoção do anel, evitando a intervenção cirúrgica e reduzindo a possibilidade de reganho de peso. / Ring dysfunction after roux-en-y gastric bypass (RYGB) causing delayed gastric emptying on Fobi pouch is classically treated by surgical ring removal. In a novel way of using selfexpandable stents, intraluminal erosion of the ring is achieved, allowing its removal by endoscopy, with no need of surgery. No study has shown clinical applicability of this principle in RYGB banded with silastic ring. In this case series we analyze endoscopic removal of noneroded dysfunctional rings after RYGB using self-expandable plastic stents (SEPS). This is a prospective case series of 41 patients with delayed gastric emptying secondary to extrinsic compression of the ring after RYGB between 2007 and 2013. Successful ring removal, symptoms improvement, weight control and adverse events were evaluated. Mean age of subjects was 44.1 years, median BMI at treatment was 27.0 Kg/m2. Most common symptom was vomiting (n=37), with daily occurrence in 46.3%. Success was defined as symptoms improvement after stent and ring removal. SEPS placement was done under general anesthesia and fluoroscopic guidance. A standard gastroscope (Pentax Medical, Montvale, NJ), and a PolyflexTM stent (25x21x150mm) (Boston Scientific, Natick, MA) were used in all cases. All patients were discharged after a 2-hour observation period, with liquid diet and proton pump inhibitor. SEPS induced complete erosion in 24 patients, allowing for simultaneous stent and ring removal. The median time of stenting was 15 days. There was one case of stent migration, which was naturally expelled. Most common adverse event was vomiting (n=7). There was no early stent removal, and no serious complications. After a mean follow-up of 6 months, there was no significant change in mean BMI, and 78% of patients are able to ingest solid foods. Endoscopic stents led to ring intraluminal erosion in 100% of subjects, allowing for successful removal of dysfunctional rings. The procedure is technically feasible and safe, with a 29.3% occurrence of mild adverse events (vomiting), and no serious complications. It proved to be a reasonable alternative for ring removal in our casuistic, avoiding surgery, and decreasing the possibility of weight regain.

Le DT2 est caractérise par un défaut combiné de la sécrétion et de l’action de l’insuline. Depuis près d’un demi siècle la chirurgie bariatrique et notamment le Roux-en-Y Gastric Bypass (RYGB) ont montré des effets spectaculaires sur le contrôle glycémique remettant en question le paradigme de la prise en charge médicale du DT2. L’exclusion gastro duodénale induite par le RYGB améliore le métabolisme glucidique indépendemment de la perte de poids. Ainsi les modifications du flux biliaire semblent jouer un rôle, cependant les mécanismes sous-jacents ne sont pas clairs. Nous avons réalisés des RYGB chez le miniporc et nous avons montré que l'absorption intestinale du glucose est diminuée dans l’anse alimentaire (AL) dépourvue de bile. L'absorption du glucose dans l’AL était restaurée par l'ajout de la bile, et cet effet était inhibé lorsque le co transport actif sodium glucose 1 (SGLT1) était bloquée par la phlorizine. SGLT1 restait exprimée dans la AL, cependant la teneur dans la lumière de l’intestin en sodium était nettement diminuée. L’ajout de sodium dans l'AL provoquait le même effet que la bile sur l'absorption du glucose et augmentait également l’excursion glycémique post prandiale chez le miniporc au cours d’un repas test vigil. La diminution de l'absorption intestinale du glucose après RYGB a ensuite été confirmée chez l'homme. Nos résultats démontrent que la l’exclusion biliaire affecte le métabolisme post prandiale du glucose par modulation des co transporteurs intestinaux sodium-glucose. / Type 2 diabetes (T2D) is characterized primarily as a combined defect of insulin secretion and insulin action. For nearly a decade, the somewhat mysterious but spectacular benefit of metabolic surgery, and more specifically of Roux-en-Y gastric bypass (RYGB), on glucose control has been caused a questioning the current paradigm of T2D management. Gastro-intestinal exclusion by RYGB improves glucose metabolism, independent of weight loss. Although changes in intestinal bile trafficking have been shown to play a role, the underlying mechanisms are unclear. We performed RYGB in minipigs and showed that the intestinal uptake of ingested glucose is blunted in the bile deprived alimentary limb (AL). Glucose uptake in the AL was restored by the addition of bile, and this effect was abolished when active glucose intestinal transport was blocked with phlorizin. Sodium-glucose cotransporter 1 remained expressed in the AL, while intraluminal sodium content was markedly decreased. Adding sodium to the AL had the same effect as bile on glucose uptake. It also increased postprandial blood glucose response in conscious minipigs following RYGB. The decrease in intestinal uptake of glucose after RYGB was confirmed in humans. Our results demonstrate that bile diversion affects postprandial glucose metabolism by modulating sodium-glucose intestinal cotransport.

Η γαστρική παράκαμψη κατά Roux en Y αποτελεί την πλέον δημοφιλή επέμβαση αντιμετώπισης της νοσογόνου παχυσαρκίας. Στη σύγχρονη εποχή, πάνω από τις μισές επεμβάσεις γαστρικής παράκαμψης διενεργούνται λαπαροσκοπικά. Σκοπός της παρούσας μελέτης είναι η σύγκριση μεταξύ της ανοικτής και της λαπαροσκοπικής τεχνικής, σε χρονικό ορίζοντα παρακολούθησης 5 ετών από την επέμβαση. Μέθοδος: Οι πρώτοι 60 ασθενείς, που υποβλήθηκαν σε ανοικτή γαστρική παράκαμψη και οι αντίστοιχοι 60 ασθενείς, που υποβλήθηκαν σε λαπαροσκοπική επέμβαση, μελετήθηκαν για 5 χρόνια μετεγχειρητικά. Οι παράμετροι, που καταγράφηκαν περιελάμβαναν την απώλεια βάρους και τη διατήρηση αυτής, τη βελτίωση ή πλήρη ίαση των συνοδών της παχυσαρκίας νόσων, τις πρώιμες και όψιμες μετεγχειρητικές επιπλοκές, τη διάρκεια επέμβασης και το χρόνο νοσηλείας των ασθενών. Αποτελέσματα: Όλοι οι ασθενείς παρουσίασαν απώλεια βάρους, χωρίς να παρατηρούνται στατιστικά σημαντικές διαφορές μεταξύ των δύο ομάδων, που διατηρήθηκε σε όλη τη διάρκεια του follow-up. Μικρή επανάκτηση του απολεσθέντος βάρους παρατηρήθηκε μετά τον 3ο χρόνο μετεγχειρητικά. Η ίαση ή βελτίωση των συνοδών νοσημάτων δεν παρουσίασε στατιστικά σημαντική διαφορά μεταξύ των δύο ομάδων. Ισοδύναμες παρουσιάζονται και οι δύο τεχνικές, όσον αφορά στην εμφάνιση μετεγχειρητικών επιπλοκών. Η διάρκεια της λαπαροσκοπικής επέμβασης παρουσιάζεται μεγαλύτερη, γεγονός που μπορεί να ερμηνευθεί βάσει της καμπύλης εκμάθησης. Η διάρκεια νοσηλείας δεν παρουσιάζει διαφορά μεταξύ των δύο ομάδων. Συμπεράσματα: Η λαπαροσκοπική γαστρική παράκαμψη, συγκρινόμενη με την ανοικτή επέμβαση, αποτελεί μία εξίσου ασφαλή και αποτελεσματική τεχνική για την αντιμετώπιση της κλινικά σοβαρής παχυσαρκίας. / Roux en Y gastric bypass (RYGBP) is the most popular operation between patients, undergoing bariatric operation. In modern times, over half of the gastric bypass operations are performed by the laparoscopic way. The aim of the present study is the comparison between open and laparoscopic technique, in a follow-up period of 5 years post surgically.`Methods: The first 60 patients, who underwent open gastric bypass and the respective 60 patients, who underwent the laparoscopic approach, were studied for 5 years post surgically. The parameters recorded, included the excess weight loss and the following maintenance of the loss, the improvement or healing of the obesity related comorbidities, early and late complications, the duration of the operation and the duration of the patients’ hospitalization. Results: All patients exhibited excess weight loss, without statistically significant differences between the two groups, which maintained throughout the follow-up period. A small proportion of regaining the lost weight was observed after the 3rd year post surgically. Healing or improvement of the obesity related comorbidities didn’t appear statistically significant difference between the two groups. There were no differences between the two groups regarding the post surgically complications. The duration of the laparoscopic approach was longer, which can be attributed to the learning curve. The duration of the patients’ hospitalization didn’t differ between the two groups. Conclusion: Laparoscopic gastric bypass, compared to the open procedure, is an equally safe and effective technique for the confrontation of clinically severe obesity.

<p>This thesis examines the effect of surgical weight loss on gut and adipose tissue peptides involved in appetite regulation and energy homeostasis in morbidly obese humans. Roux-en-Y gastric bypass (RYGBP) is the gold standard operation used for effective long-term weight loss and improved health. The exact mechanisms for this outcome are under investigation.</p><p>We measured ghrelin, a recently discovered hunger hormone, insulin, adiponectin and leptin along with anthropometry measures in 66 morbidly obese patients prior to and 6 and 12 months after RYGBP. Impressive weight loss occurred postoperatively as did alterations in the peptides. Consistent correlations were found between weight, leptin, ghrelin and insulin. The main findings were low ghrelin concentrations in obesity and an increase after RYGBP.</p><p>We explored inflammatory proteins C-reactive protein (CRP), serum amyloid A and interleukin-6 before and during massive weight loss 6 and 12 months after RYGBP in morbidly obese subjects. The studied proteins declined after surgery and a correlation between CRP and homeostatic model of assessment for insulin resistance, independent of BMI, strongly linked insulin resistance and inflammation. CRP declined most in insulin-sensitive subjects.</p><p>We examined the excluded stomach mucosa and vagus nerve by measuring gastrin, pepsinogen I (PGI), pancreatic polypeptide (PP) and ghrelin levels during week 1 and year after RYGBP. Ghrelin levels rose with weight loss but declined 24-hours after surgery, like PP, indicating transient vagal nerve damage. Low levels of gastrin and PGI suggest a resting mucosa.</p><p>We evaluated gut peptides: peptide YY (PYY), glucaogon like peptide-1 (GLP-1), pro-neurotensin (pro-NT) and PP, in lean (young and middle-aged), obese and postoperative RYGBP subjects pre- and postprandially. RYGBP subjects had exaggerated levels of PYY and GLP-1 postprandially and higher basal proNT levels, implying a ‘satiety peptide tone’ that may contribute to the maintenance of weight loss.</p><p>In summary, RYGBP results in marked weight loss and alterations in gut and adipose tissue peptides involved in appetite regulation and energy homeostasis. These postoperative peptide changes may contribute to impressive weight loss observed after RYGBP.</p>

Most patients with pancreatic cancer will present with metastatic or locally advanced disease. Unfortunately, most patients with localized disease will experience recurrence even after multimodality therapy. As such, pancreatic cancer patients arrive at a common endpoint where decisions pertaining to palliative care come to the forefront. This article summarizes surgical, endoscopic, and other palliative techniques for relief of obstructive jaundice, relief of duodenal or gastric outlet obstruction, and relief of pain due to invasion of the celiac plexus. It also introduces the utility of the palliative care triangle in clarifying a patient's and family's goals to guide decision making.

INTRODUÇÃO: O diabetes mellitus tipo 2 (DM2) é uma doença correlacionada com a obesidade mórbida. O paciente obeso apresenta efeito incretínico suprimido e consequente desbalanço da homeostase glicêmica. Diversos estudos evidenciam a melhora do DM2 após a confecção da Gastroplastia com derivação intestinal em Y de Roux (GDYR). Os mecanismos de controle da glicemia podem ser de longo e curto prazo. Os mecanismos de ação precoce estão ligados à restrição calorica, melhora da resistência insulínica, da função da célula beta pancreática e retorno do efeito incretínico pelo aumento do GLP1 e GIP, porém os dados são conflitantes. MÉTODOS: Onze pacientes obesos graves diabéticos foram submetidos à GDYR com confecção de gastrostomia no remanescente gástrico após perda de peso inicial de 10%. Os pacientes foram submetidos à coleta de entero-hormônios, perfil glicêmico e Teste de Tolerância Oral à glicose (TTOG) no pré-operatório em curva temporal que foi comparado ao pós-operatório por Via Oral e por Via da Gastrostomia em até 7 dias após o procedimento. RESULTADOS: A média da idade foi 46,09±7,08 anos. No pré-operatorio, o peso médio foi 120,97±17,02 quilogramas, altura 1,67±0,11 metros, IMC médio 44,06±6,59 kg/m2, glicemia de jejum média 194,55±62,45 mg/dl e hemoglobina glicada 8,74±1,64%. Em 77,7% dos pacientes, houve remissão precoce do DM2 no pós-operatório avaliado pelo TTOG. Também foi observada queda significante da glicemia, insulinemia e do HOMA-IR independente da via administrada. Ocorreu aumento significativo do GLP1 e redução do GIP pela Via Oral pós-operatória. A Grelina não apresentou alterações. CONCLUSÃO: Evidenciou-se redução da glicemia e da resistência periférica nos primeiros dias de pós-operatório da GDYR, independente da via de passagem do alimento. A alteração no efeito incretínico (aumento do GLP1 e redução do GIP) só foi observada na Via Oral pós-operatória / INTRODUCTION: Type 2 diabetes mellitus (DM2) is a disease correlated with morbidly obesity. The obese patient has a suppressed incretin effect and consequent inbalance of glycemic homeostasis. Several studies have shown an improvement in DM2 after Gastroplasty with Roux-en-Y gastric bypass (RYGB). The mechanisms of glycemic control may be long-term and shortterm. The mechanisms of early action are linked to caloric restriction, improvement of insulin resistance, pancreatic beta cell function and return of the incretin effect through the increase of GLP1 and GIP, but the data are conflicting. METHODS: Eleven diabetic obese patients underwent RYGB with gastrostomy in gastric remnant after initial 10% weight loss. Patients were submitted to assessment of enterohormones, glycemic profile and Oral Glucose Tolerance Test (OGTT) in the preoperative period in a time curve that was compared to the postoperative period by Oral Via and Gastrostomy Via up to 7 days after the procedure .RESULTS: The mean age of the group was 46.09 ± 7.08 years. In the preoperative the mean weight was 120.97 ± 17.02 kilograms, height of 1.67 ± 0.11 meters, mean BMI of 44.06 ± 6, 59 kg/m2, mean fasting blood glucose of 194.55 ± 62.45 mg/dl and glycated hemoglobin 8.74 ± 1.64%. In 77.7% of the patients there was remission of DM2 in postoperative evaluated by the OGTT. Significant decrease in glycemia, insulinemia and HOMA-IR was also observed, regardless of the route of administration. There was a significant increase in GLP1 and reduction of GIP by the postoperative oral route. Ghrelin did not change. CONCLUSION: A reduction in glycemia and peripheral insulinal resistance was observed in early postoperative days of RYGB, independent of the food route. The change in incretin effect (increase of GLP1 and reduction of GIP) was only observed in the postoperative oral route

O leite é essencial para o desenvolvimento pós-natal da mucosa gástrica e durante o período de aleitamento, o jejum estimula a proliferação celular. Mostramos que o TGF<font face=\"Symbol\">b, reverte este efeito e p27 está envolvida neste mecanismo. Os níveis de p27 oscilam durante o ciclo celular, devido à sua fosforilação na Thr187, que leva à degradação pelo sistema UPS. Diferentes estudos relatam que TGF<font face=\"Symbol\">b pode aumentar p27, através do controle de sua degradação. Este estudo visa analisar o efeito do jejum e TGF<font face=\"Symbol\">b1, na regulação de p27 no epitélio gástrico de ratos lactentes. Para tanto, filhotes de 14 dias foram submetidos a jejum durante 90 min e receberam uma dose única de TGF<font face=\"Symbol\">b ou PBS, por gavagem. As amostras foram coletadas após 2 e 14 horas de tratamento. Analisamos a concentração proteica de p27, fosfo-p27, Skp2 e Cdh1. Observamos que durante o jejum houve a diminuição de p27 e Cdh1, paralelamente ao aumento de fosfo-p27 e Skp2. Enquanto que o tratamento com TGF<font face=\"Symbol\">b1, reverteu os efeitos do jejum em 2h e 14h em todas as proteínas analisadas. Além disso, o jejum aumentou a ubiquitinação e degradação de p27 e o tratamento com TGF<font face=\"Symbol\">b1 reverte esses efeitos. Desta forma, o TGF<font face=\"Symbol\">b1 do leite materno estabiliza os níveis de p27 e assim, influenciar a progressão do ciclo celular no epitélio gástrico. / Milk is essential for postnatal development of the gastric mucosa and during the suckling period fasting stimulates cell proliferation. We have shown that TGF<font face=\"Symbol\">b reverses this effect and p27 is involved in this mechanism. The levels of p27 oscillate during the cell cycle due to its phosphorylation at Thr187, which leads to its degradation by the UPS. Different studies reported that TGF<font face=\"Symbol\">b can increase p27, by controlling its degradation. This study aims to analyze the effect of fasting and TGF<font face=\"Symbol\">b1 in regulating p27 in lactating rats gastric epithelium. For such, the 14 days rats were fasted for 90 min and received a single dose of TGF<font face=\"Symbol\">b or PBS by gavage. Samples were collected after 2 and 14 hours of treatment. We analyzed the p27 protein concentration, phospho-p27, Skp2 and Cdh1. We found that during fasting, p27 and Cdh1 a decreased, at the same time to the increment of phospho-p27 and Skp2. The treatment with TGF<font face=\"Symbol\">b1, reversed the effects of fasting on 2h and 14h in all proteins analyzed. Moreover, the fasting increased the ubiquitination and the degradation of p27, while TGF<font face=\"Symbol\">b1 treatment reversed these effects. Thus the milk born TGF<font face=\"Symbol\">b1 can stabilize p27 levels and thus influences cell cycle progression in lactent rat gastric epithelium.