O câncer gástrico é a terceira causa de morte por câncer no mundo e a quimioterapia combinatória é um dos principais tratamentos para esta doença. Contudo, a principal causa de falha do tratamento é a quimiorresistência. Considerando este obstáculo juntamente com a descoberta de que muitas proteínas envolvidas na mitose podem estar associadas à tumorigênese, vários agentes antimitóticos estão sendo desenvolvidos e testados. As proteínas mitóticas AURKB e NDC80 foram recentemente identificadas como proteínas potenciais a serem inibidas no câncer gástrico. Portanto, o objetivo deste estudo foi analisar os efeitos da inibição de AURKB e NDC80 pelos fármacos experimentais ZM447439 e INH1, respectivamente. Analisamos os efeitos em duas linhagens de adenocarcinoma gástrico avaliando expressão gênica, ciclo celular, morte celular, análise morfométrica nuclear, capacidade de migração e presença de células-tronco tumorais. É importante enfatizar que essas duas pequenas moléculas não foram testadas na quimioterapia do câncer gástrico até o momento. Além disso, após uma revisão da literatura, concluímos que os melhores resultados dos ensaios clínicos foram alcançados quando antimitóticos foram combinados com a terapia convencional. Dessa forma, avaliamos também os efeitos da associação de 5- FU com ZM447439. Nossos resultados demonstraram que a monoterapia com 5-FU, ZM447439 e INH1 induziu a expressão gênica diferencial nas linhagens de câncer gástrico (ACP02 e ACP03) de pelo menos 22 de um total de 82 genes envolvidos em várias vias, como apoptose, ciclo celular, senescência e transição epitélio-mesenquimal. Observamos também que ZM447439 e sua combinação com 5-FU induziram apoptose, catástrofe mitótica, senescência e ciclo celular alterado nas linhagens de câncer gástrico. Outro dado interessante foi a expressão dos marcadores de células-tronco tumorais gástricas, LGR5 e CD24, e a capacidade de formar esferas, indicando que ambas ACP02 e ACP03 podem conter células tronco tumorais. Além disso, a monoterapia com ZM447439 ou 5-FU foi capaz de inibir a formação de esferas. Por outro lado, o INH1 mostrou menor atividade antitumoral, uma vez que apresentou o maior valor de IC50 e foi capaz somente de induzir apoptose e reduzir a migração celular. Interessantemente, a combinação do 5-FU com ZM447439 permitiu o uso de doses menores dos compostos, além de ser capaz de induzir a apoptose num tempo mais curto quando comparado com o tratamento com os fármacos isolados. Em síntese, os resultados observados sugerem o inibidor de AURKB, ZM447439, e sua associação com o agente quimioterápico 5-FU, como tratamentos promissores do câncer gástrico com base em sua elevada atividade antitumoral in vitro. / Gastric cancer is the third cause of cancer death worldwide and combinatorial chemotherapy is one of the main treatments for this disease. However, the major cause of treatment failure is chemoresistance. Considering this obstacle together with the discovery that many proteins involved in mitosis might be associated to tumorigenesis, several new anti-mitotics are being developed and tested. The mitotic proteins AURKB and NDC80 were recently shown as potential proteins to be inhibited in gastric cancer. Therefore, the aim of this study was to analyze the effects of AURKB and NDC80 inhibition by the experimental drugs ZM447439 and INH1, respectively. We analyzed the effects in two gastric adenocarcinoma cell lines evaluating gene expression, cell cycle, cell death, nuclear morphometric analysis, migration ability and presence of gastric cancer stem cells. It is important to emphasize these two small molecules have not been tested in gastric cancer chemotherapy until now. Moreover, after reviewing the literature, we concluded the best results of clinical trials were achieved when anti-mitotics were combined with conventional therapy. Thus, we evaluated the effects of 5-FU and ZM447439 combination as well. Our results demonstrated that monotherapy with 5-FU, ZM447439 and INH1 induced differential gene expression in gastric cancer cell lines (ACP02 and ACP03) of at least 22 from 82 genes involved in several pathways such as apoptosis, cell cycle, senescence and epithelial mesenchymal transition. We also observed that ZM447439 and its combination with 5-FU induced apoptosis, mitotic catastrophe, senescence and altered cell cycle in gastric cancer cell lines. Another interesting data was the expression of the gastric cancer stem cell markers LGR5 and CD24, and the ability to form spheres, indicating that both ACP02 and ACP03 may be composed by cancer stem cells. Furthermore, monotherapy with either ZM447439 or 5-FU were capable of inhibiting the formation of spheres. On the other hand, INH1 have shown lower antitumoral activity since it presented the highest IC50 value and was only capable of inducing apoptosis and reducing cell migration. Interestingly, the combination of 5-FU with ZM447439 allowed the use of smaller doses of the compounds, in addition to being able to induce apoptosis in a shorter time when compared to the treatment with the isolated drugs. Taken together, our findings suggest that due to the high antitumoral activity shown by ZM447439 and mainly its association with 5-FU, these might be promising gastric cancer therapies.

Introduction: The incidence of gastro-oesophageal cancers has increased considerably over the last decade. As the disease is associated with a poor prognosis, there is a need to identify markers of treatment response which could be used in the future to improve the management of gastro-oesophageal tumours. Aims: 1) To compare the ability of published histological grading criteria (Becker, Mandard and Ninomiya) to assess response to neo-adjuvant chemotherapy (NCT) in gastro-oesophageal cancers. 2) To evaluate the expression of thymidylate synthase (TS) in pre-treatment diagnostic biopsy samples as a predictive marker of response to NCT. 3) To investigate whether measurements of hypoxia obtained using pimonidazole are prognostic for treatment outcome in patients with gastro oesophageal adenocarcinoma (ACC). 4) To study the prognostic significance and clinicopathological associations of epithelial mesenchymal transition (EMT) related proteins S100A4, Vimentin and Snail1 in gastro-oesophageal junction (GOJ) tumours. 5) To evaluate the ability of dynamic contrast enhanced (DCE) MRI to assess chemoradiotherapy (CRT) induced changes in oesophageal cancer. Methods: 1) Formalin fixed paraffin embedded (FFPE) tumour blocks and haematoxylin and eosin stained slides of samples from resected tumours (n=66) were obtained from patients who received NCT for gastric and GOJ tumours. The slides were scored independently by two observers and kappa scores calculated. 2) Pre-treatment diagnostic tissue biopsy samples were obtained from 45 patients with gastric and GOJ cancer who received NCT. TS expression was assessed using immunohistochemistry (IHC) and scored by two observers. The clinical and pathological data were analysed. 3) 57 patients were prospectively administered intravenous pimonidazole and the tumour specimens were collected both at staging laparoscopy and resection. IHC was performed to assess pimonidazole expression and determine its association with clinico-pathological factors. 4) Tissue microarrays were prepared from resection specimens from GOJ ACC. IHC was performed to investigate EMT related protein expression. 5) DCE-MRI was performed on five patients diagnosed with oesophageal cancer treated with CRT. Multiple pharmacokinetic parameters were evaluated. Findings: 1) Becker's histological grading criteria was the most reproducible and prognostic of outcome. The incidence of complete histological response (5%) was low in patients receiving NCT. 2) No prognostic benefit of TS expression was identified. 3) Results from only 34 patients were available for analysis. 77% pimonidazole positivity was observed. Preoperative anaemia was associated with significant tumour pimonidazole expression (p=0.04). Pimonidazole was not prognostic for outcome. 4) The overall positive expression was S100A4 (85%), Vimentin (14%) and Snail1 (89%). The increased expression of S100A4 at the tumour body (p=0.02) and luminal surface (p=0.01) was associated with a poor outcome. 5) Significant changes were measured in DCE-MRI pharmacokinetic parameters after CRT. Conclusion: 1) Becker's histological response grading criteria should be further studied in routine clinical practice for response assessment to NCT. 2) TS should be explored further as a marker of NCT response in gastro-oesophageal cancer. 3) Hypoxia is a characteristic feature of upper gastrointestinal ACC and is associated with anaemia. 4) S100A4 is the most useful marker of EMT in GOJ adenocarcinoma. 5) DCE-MRI tracer kinetic parameters should be explored in a larger study to assess their ability to monitor the efficacy of and predict response to neo-adjuvant treatment.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A Plumeria rubra L. à uma planta laticÃfera pertencente à famÃlia Apocynaceae, popularmente conhecida como Jasmim. Esta amplamente distribuÃda em regiÃes tropicais e subtropicais, incluindo o Brasil. Essa planta à utilizada popularmente para o tratamento de sÃfilis, febre e como purgativo. Alguns estudos mostram que o lÃtex de P. rubra possui atividade antioxidante e vasodilatadora. O objetivo desse trabalho foi avaliar o efeito gastroprotetor das proteÃnas laticÃferas da Plumeria rubra (PrLP) em modelo de Ãlcera gÃstrica induzida por etanol, investigar o possÃvel envolvimento dos receptores TRPV1, da via NOGMPcKATP e da glutationa, e possÃveis efeitos tÃxicos. A manipulaÃÃo dos animais e os protocolos experimentais foram registrados no Comità de Ãtica Institucional sob o nÃmero 057/2010. Camundongos Swiss (n = 8), em jejum de 16h, foram tratados por via intravenosa com PrLP nas doses de 0,05; 0,5; 5 e 50 mg/kg. ApÃs 30 min da administraÃÃo de PrLP os animais receberam 0,2 ml de etanol absoluto v.o. Decorridos 60 min dessa administraÃÃo, os animais foram sacrificados, os estÃmagos removidos e analisados para determinaÃÃo do Ãndice de lesÃo. Para investigar o envolvimento de mediadores no efeito de PrLP, os animais receberam indometacina (10 mg/kg; v.o.), L-NAME (20 mg/kg; i.p.), ODQ (10 mg/kg; i.p.), glibenclamida (5 mg/kg; i.p.) e capsazepina (5 mg/kg; i.p) antes do tratamento com PrLP (0,5 mg/kg; i.v.). Misoprostol (50 Âg/kg v.o), L-arginina (600 mg/kg; i.p.), diazÃxido (3mg/kg; i.p.) e capsaicina (0,3 mg/kg; v.o.) foram utilizados como droga-padrÃo. Para avaliar o efeito de PrLP sobre os nÃveis de NO3-/NO2, foi realizada sua dosagem no homogenato do estÃmago, mas para investigar um possÃvel efeito antioxidante, foi realizada a dosagem dos nÃveis de GSH em estÃmagos normais e lesionados. Para a toxicidade sub-crÃnica os animais foram tratados por 7 dias com a dose de 50 mg/kg; i.v., seguido da avaliaÃÃo de vÃrios parÃmetros, tais como: peso corporal, hemograma completo, bioquÃmicos (urÃia, ALT e AST) e peso Ãmido de ÃrgÃos vitais (coraÃÃo, baÃo, fÃgado e rim). PrLP nas doses de 0,5; 5 e 50 mg/kg foi capaz de inibir lesÃo gÃstrica em 81,9; 72,8 e 68%, respectivamente, recuperou os nÃveis de GSH na mucosa em 105% quando comparados com o grupo etanol e nÃo alterou os nÃveis de GSH em animais que nÃo tiveram seus estÃmagos lesionados pelo etanol. Adicionalmente, PrLP tambÃm aumentou em 26% os nÃveis de NO3-/NO2- que foram reduzidos pela administraÃÃo de etanol. Indometacina, L-NAME, ODQ, Glibenclamida e capsazepina foram capazes de reverter o efeito de PrLP, demonstrando o envolvimento das Prostaglandinas, NO, GMPc, canais de KATP e dos receptores TRPV1 em seu mecanismo de aÃÃo. AlÃm disso, o tratamento por 7 dias com PrLP nÃo alterou nenhum parÃmetro avaliado, mostrando seguranÃa no seu uso. Estes resultados indicam que PrLP possui atividade farmacolÃgica gastroprotetora sobre a mucosa do estÃmago ao qual parece ser mediada em parte pela modulaÃÃo de prostaglandina, pela via NO/GMPc/KATP e pelos receptores TRPV1, ao qual possuem papel fundamental na manutenÃÃo do fluxo sanguÃneo e na defesa da mucosa gÃstrica. PrLP atua evitando a depleÃÃo dos nÃveis de GSH induzidas pelo etanol. Sendo isto importante para a manutenÃÃo das defesas antioxidantes da mucosa. AlÃm do mais, PrLP nÃo apresenta toxicidade aguda nos animais. / The Plumeria rubra is a laticifer plant of family Apocynaceae, popularly known as âJasmimâ. It is widely distributed in tropical and subtropical regions, including Brazil. This plant is commonly used for the treatment of syphilis, fever, and as a purgative. Some studies show that the latex of P. rubra has antioxidant and vasodilator activity. The aim of this study was to evaluate the gastroprotective effect of laticifers proteins of Plumeria rubra (PrLP) in ethanol-induced gastric damage, to investigate the possible involvement of TRPV1 receptors, NOcGMPKATP pathway and glutathione, and possible toxic effects. Animal handling and experimental protocols were registered on the Institutional Ethics Committee under number 057/2010. Swiss mice (n=8), fasting for 16 hours, were treated intravenously (i.v.) with PrLP doses of 0.05, 0.5, 5 and 50 mg/kg. After 30 min the animals received 0.2 ml of absolute ethanol per oral (p.o.). After 60 min of ethanol administration, the animals were sacrificed, their stomachs removed and analyzed to determine lesion index. To investigate the involvement of mediators in PrLP effect, animals received indomethacin (10 mg/kg, p.o.), L-NAME (20 mg/kg, i.p.), ODQ (10 mg/kg, i.p.), glibenclamide (5 mg/kg, i.p.) and capsazepine (5 mg/kg, i.p.) prior to treatment with PrLP (0.5 mg/kg i.v.). Misoprostol (50 Âg/kg; p.o.), L-arginine (600 mg/kg; i.p.), diazoxide (3 mg/kg; i.p.) and capsaicin (0.3 mg/kg; p.o.) were used as standard-drug. To evaluate the effect of PrLP on the levels of NO3-/NO2, the dosage was performed in the homogenate of the stomach, but to investigate a possible antioxidant effect, it was carried out the measurement of the GSH levels in normal and injured stomachs. For sub-chronic toxicity animals were treated for 7 days with 50 mg/kg i.v., followed by evaluation of various parameters, such as: body weight, complete blood count, biochemical (urea, ALT, AST) and wet weight of vital organs (heart, spleen, liver and kidney). PrLP at doses of 0.5, 5 and 50 mg/kg was able to inhibit the gastric lesions by 81.9, 72.8 and 68%, respectively, retrieving the GSH levels in the mucosa by 105% compared with the ethanol group and PrLP did not alter the GSH levels in animals that were not ethanol-lesioned stomachs. Additionally, PrLP also increased in 26% NO3-/NO2- levels that were reduced by ethanol administration. Indometacin, L-NAME, ODQ, glibenclamide and capsazepine were able to reverse the PrLP protective effect, demonstrating the involvement of prostaglandins, NO, GMPc, potassium channels ATP-dependent and TRPV1 receptors in its mechanism of action. Furthermore, the treatment for 7 days with PrLP did not change any parameter evaluated showing safety in their use. These results indicate that PrLP have gastroprotective pharmacology activity on the gastric mucosa which seems to be mediated in part by modulation of prostaglandin, NO/cGMP/KATP pathway and TRPV1 receptors, which play a fundamental role in maintaining blood flow and gastric mucosa defense. PrLP acts avoiding depletion of GSH levels ethanol-induced. Since this is important for the maintenance of mucosal antioxidant defenses. Moreover, PrLP did not shown acute toxicity in animals.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Ulcer can be defined as a chronic inflammatory disease of the stomach and duodenum, which appears as a lesion in the digestive tract, which extends through the mucosa muscle or more deeply. The ulcer usually occurs because of an imbalance between protective and agrssive factors of the mucosa. Esculin (ESC) (6.7-Dihydroxycoumarin-6-O-Glucoside) was evaluated in models ethanol or indomethacin-induced gastric lesions in mice. Esculin (12.5, 25 and 50 mg/kg, p.o.) significantly reduced gastric lesions induced by absolute ethanol (0.2 mL/animal) at 69.96, 72.94 and 79.33% respectively, showing no relationship dose-response at the doses studied. This gastroprotection was also evaluated microscopically showing that the ESC (25 mg/kg, p.o.) decreased the cell loss in the mucosa, submucosal edema and hemorrhage. Esculin (25 and 50 mg/kg, p.o.) also reduced significantly the gastric lesions induced by indomethacin (20 mg/kg, p.o.). Gastroprotective mechanism of ESC was examined in the dose of 25 mg/kg, in the model of gastric lesions induced by ethanol in mice. In animals pretreated with L-NAME (10 mg/kg, sc), an inhibitor of nitric oxide synthase, or with glibenclamide (5 mg/kg, i.p.), a drug that blocks ATP-dependent potassium channels, or indomethacin (10 mg/kg, p.o.), a nonselective inhibitor of cyclooxygenase, the gastroprotective effect of ESC was inhibited significantly, suggesting the involvement, at least in part, of nitric oxide, activation of potassium channels and endogenous prostaglandins in gastroprotective effect of ESC. Otherwise, the gastroprotective effect of ESC (25 mg/kg, p.o.) was not reversed in animals pretreated with capsazepine (5 mg/kg, i.p.), an antagonist of vanilloid receptor TRPV-1, demonstrating that there is activation of these receptors in the mechanism of action of ESC. This work was also evaluated the antioxidant mechanism of ESC as gastroprotective agent, against ethanol-induced lesions. Under our experimental conditions, the model of induction of ethanol injury caused changes in the antioxidant system of the gastric mucosa of mice as the decrease in the levels of sulfhydryl groups (GSH) and activity of superoxide dismutase (SOD), also showed increased activity catalase (CAT), the activity of myeloperoxidase (MPO) and the concentration of species that react with thiobarbituric acid (TBARS) as index of lipid peroxidation (LPO). Esculin in the model of ethanol did not interfere with the concentration of GSH, but increased SOD activity, allowed the restoration of normal CAT activity, normal levels of LPO and MPO activity. The data suggest that the ESC promotes gastroprotection against gastric lesions induced by ethanol or indomethacin in mice whose mechanisms include the involvement of endogenous prostaglandins, nitric oxide, and or, of KATP channels, as well as an antioxidant activity. / A Ãlcera pÃptica pode ser definida como sendo uma doenÃa inflamatÃria crÃnica do estÃmago e duodeno, que se apresenta como uma lesÃo na mucosa do trato digestivo, que se estende atravÃs da musculatura da mucosa ou mais profundamente. A Ãlcera pÃptica geralmente ocorre devido a um desequilÃbrio entre os fatores de defesa e agressores da mucosa. Este trabalho teve como objetivo avaliar a atividade gastroprotetora da esculina, (6,7-diidroxicumarina-6-o-glicosÃdio), e identificar os mecanismos farmacolÃgicos envolvidos. A esculina foi avaliada em modelos de lesÃes gÃstricas induzidas por etanol absoluto (0,2 mL/animal) em camundongos swiss, nas doses 12,5, 25 e 50 mg/kg, v.o., os resultados mostraram a reduÃÃo das lesÃes gÃstricas induzidas por etanol em 69,96, 72,94 e 79,33 % respectivamente, nÃo mostrando relaÃÃo dose-resposta nas doses estudadas. Esta gastroproteÃÃo tambÃm foi avaliada microscopicamente mostrando que a ESC (25 mg/kg, v.o.) diminuiu a perda celular na mucosa, formaÃÃo de edema na submucosa e hemorragia. A ESC (25 e 50 mg/kg, v.o.), tambÃm, foi avaliada no modelo de lesÃo gÃstrica induzida por indometacina (20 mg/Kg, v.o.), mostrando uma reduÃÃo das lesÃes gÃstricas. O mecanismo gastroprotetor da ESC foi analisado na sua dose de 25 mg/Kg, em modelo de lesÃes gÃstricas induzidas por etanol em camundongos. Em animais prÃ-tratados com L-NAME (10 mg/Kg, s.c.), um inibidor da Ãxido nÃtrico sintase, ou com glibenclamida (5 mg/Kg, i.p.), droga bloqueadora de canais de potÃssio ATP-dependentes, ou indometacina (10 mg/Kg, v.o.), um inibidor nÃo seletivo da ciclooxigenase, o efeito gastroprotetor da ESC foi inibido significativamente, sugerindo o envolvimento, pelo menos em parte, do Ãxido nÃtrico, ativaÃÃo dos canais de potÃssio e prostaglandinas endÃgenas no efeito gastroprotetor da ESC. De outra forma, o efeito gastroprotetor da ESC (25 mg/Kg, v.o.) nÃo foi revertido em camundongos prÃ-tratados com capsazepina (5 mg/Kg, i.p.), um antagonista dos receptores vanilÃides TRPV-1, demonstrando assim que nÃo hà ativaÃÃo destes receptores no mecanismo de aÃÃo da ESC. Neste trabalho tambÃm foi avaliado a aÃÃo antioxidante da ESC como mecanismo gastroprotetor contra as lesÃes induzidas por etanol. Sob nossas condiÃÃes experimentais, o modelo de induÃÃo de lesÃo por etanol provocou alteraÃÃo no sistema antioxidante da mucosa gÃstrica dos camundongos, como a diminuiÃÃo nos nÃveis de grupamentos sulfidrila (GSH) e atividade da superÃxido dismutase (SOD), tambÃm observamos aumento da atividade da catalase (CAT), da atividade da mieloperoxidase (MPO) e da concentraÃÃo de espÃcies que reagem com o Ãcido tiobarbitÃrico (TBARs), como Ãndice de peroxidaÃÃo lipÃdica (LPO). A ESC no modelo de etanol nÃo interferiu com a concentraÃÃo de GSH, mas aumentou a atividade da SOD, permitiu o restabelecimento da atividade normal da CAT e de patamares normais de LPO e de atividade da MPO. Os dados obtidos sugerem que a ESC promove gastroproteÃÃo contra as lesÃes gÃstricas induzidas por etanol ou indometacina em camundongos, por mecanismos que incluem o envolvimento de prostaglandinas endÃgenas, Ãxido nÃtrico, e ou, dos canais de KATP, alÃm de uma aÃÃo antioxidante.

A nutritional method commonly used to deliver feedings to premature infants is the use of a gavage tube. To measure for any undigested breastmilk or formula, a gastric aspirate is checked prior to the next feeding. There is a gap in practice as to what to do if these aspirates signify feeding intolerance. The project question centered on identifying evidence-based guidelines in the literature that would help to define best practices related to feeding intolerance of gavage-fed infants. The Johns Hopkins Nursing Evidence-Based Practice model and the Appraisal of Guidelines Research and Evaluation provided the frameworks for gathering and evaluating evidence as well as the process used in forming the practice guideline. The primary methods employed were a team approach that included a Neonatal Intensive Care Unit (NICU) Project Team and NICU expert opinion along with a literature review conducted by the doctor of nursing practice student. The NICU Project Team collected the NICU experts' input via surveys they developed and distributed as well as e-mails to authors identified from the literature review. The surveys yielded a 76% response rate from the registered nurses and a 59% response rate from the medical providers. All data collected were shared and descriptive statistics were used to evaluate the data. One of the central research findings was that gastric aspirates should no longer be routinely obtained on stable infants and, if used in evaluating feeding intolerance, they must be used in combination with other indicators. An enteral feeding guideline was developed to reflect this finding that can be shared with other NICUs and nurseries in the United States and globally to decrease the morbidity and mortality of neonates.

An assay for catheptic activity of lamb gastric tissue extract has been proposed which involves the use of a pH 3.5 hemoglobin substrate following activation of zymogens at pH 2.0, 25C for 30 min.; and inactivation at pH 8.0, 40C for 30 min thereby eliminating the effects of pepsin and rennin. Cathepsin was isolated and purified by ammonium sulfate fractionation, acetone precipitation and gel viii filtration. The purified cathepsin represented approximately 50 fold increase in specific activity over the original extract and a recovery of 15% of the original activity. Degree of purity was monitored by isoelectric focusing in polyacrylamide gels. Some characteristics of the cathepsin were determined. The purified cathepsin hydrolyzed urea-denatured hemoglobin readily at pH 3.5, but it had no activity on substrates specific for cathepsins A, B or c. a-N-benzoyloxycarbonyl- L-gutamyl-L-tyrosine, a-N-benzoyl-L-argininamide hydrochloride and a-N-acetyl-L-tyrosinamide. Approximate isoelectric point was pH 5.6. The purified enzyme was similar to cathepsin D. Parmesan, Romano, and Cheddar cheese manufactured with lamb pregastric esterase and gastric extracts added to the curd or milk were superior in flavor when both were employed, and either extract alone made better cheese than the uninoculated control.

Background: Despite a declining trend in the incidence of gastric cancer (GC), it is still a major global public health concern of the 21st century. It afflicts one million people and kills 750,000 annually. It is believed that both genetic and environmental factors contribute to the gastric carcinogenesis. However geographic variation and immigrant studies highlight the role of environmental factors. Objective: To evaluate the association of GC with the environmental factors of diet, helicobacter pylori (H. pylori) infection, lifestyle and occupation as well as family history in Iran. Methodology: A population based case-control study was conducted in the Northwest of Iran where one of the highest incidence rates of the world has been reported. Two hundred and seventeen cases of GC and 394 age and gender matched controls were recruited. Participants were interviewed using a structured questionnaire which elicited information on demographic characteristics, socioeconomic status, family and medical history, lifestyle (smoking, alcohol drinking and substance abuse) and occupation. Ten milliliters of each subject???s blood was collected for blood grouping and to investigate presence of IgG antibodies against H. pylori using an ELISA kit which had been locally validated for this study. Results: Diet and H. pylori infection were found to be the most important determinants of GC in this study. High intake of allium vegetables and fruit, especially citrus fruit, appears to play a protective role. In addition to the consumption of fruit and vegetables, consumption of fresh fish was also inversely associated with GC. On the other, hand consumption of red meat and dairy products were positively associated with the risk of GC. Other dietary practices were also found to be important factors in the etiology of GC. People who had a preference for higher salt intake and drinking strong and hot tea were at higher risk. Finally, H. pylori infection was found to increase the risk of GC. Conclusion: This study has provided important and original information about the etiology of gastric cancer particularly in the Iranian context. These findings could be used in planning preventive strategies for this malignancy, which is a major health problem in Iran.

Transpyloric flow is the final step in gastric emptying prior to intestinal absorption of nutrients and medications. The details of this process are still incompletely understood. Transpyloric flow is bi-directional, contrasting with the general perception of solely forward flow implied by studies of gross gastric emptying. The degree to which the patterns of bi-directional transpyloric flow reflect emptying of meals of varied physicochemical composition, its mechanical determinants and effect on delivery of oral medications have been evaluated by the studies presented in this thesis.

<p>Enligt WHO är övervikt en global epidemi. Gastric bypass-operationer för viktminskning blir vanligare. Syftet med studien var att undersöka psykologiska aspekter och konsekvenser av att genomgå en Gastric bypass-operation. Åtta intervjuer utfördes och analyserades med Grundad teori. Sex kategorier utformades: negativt bemötande/positivt bemötande, jag/andra, dumping som vän/dumping som fiende, att tillhöra massan/att stå ut från massan, eget ansvar/andras ansvar och bevarad självbild/förändrad självbild. Kärnkategorin kognitiv dissonans sågs genomgående i alla kategorier. Den kognitiva dissonansen reduceras genom att en eller båda kognitionerna ändras så att de bättre stämmer överens eller genom att överbryggande kognitioner läggs till. Studiens kärnkategori, kognitiv dissonans, leder till tanken att för att operationen skall vara framgångsrik långsiktigt bör den opererade: 1) se sig som ansvarig för viktnedgången, 2) se sig som en smal/normalviktig individ och 3) tro att den är värd framgång.</p>

<p>Roux-en-Y gastric bypass (RYGBP) sustains weight loss and ameliorates diseases common in the morbid obese (BMI>40 kg/m²), but leaves the stomach and duodenum inaccessible. Morbidly obese patients have increased operative risks and in other fields minimal surgery is known to facilitate the postoperative course.</p><p>The aim of this thesis was to evaluate hand-assisted laparoscopy in RYGBP and develop techniques to study the excluded stomach.</p><p>The hand-assisted technique was developed in 13 patients and subsequently compared to open surgery in a blinded, prospective, randomised trial of 50 patients.</p><p>Hand-assistance was feasible with a low need for conversions or re-operations. The duration of surgery was longer (150 versus 85 minutes) and postoperative results were similar to those in open surgery. Thus, the patients did not appear to derive benefits from hand-assisted laparoscopy. Interventional radiology accessed the excluded stomach and allowed endoscopy, barium studies and acid measurements. Chronic gastritis and low acid production were found. After RYGBP, 8 of 22 patients (36%) had duodenogastric bile reflux (DGBR), when studied by HIDA-scintigraphy. No DGBR was seen among controls. The gastric mucosa was evaluated by serology</p><p>(pepsinogen I (PGI), H. pylori and H,K-ATPase) in 64 patients before and 1-4 years after operation. RYGBP, in contrast to gastric restriction, had reduced PGI levels postoperatively. According to serology, the mucosa is atrophic or in a resting state.</p><p>This study focuses on safety in RYGBP. Hand-assisted laparoscopy was feasible, but not favourable compared to an optimised open procedure. The excluded stomach is no longer inaccessible and characterised by chronic gastritis, low acid production and frequent bile reflux.</p>