CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / O (-)-α-bisabolol, em doses de 100 e 200 mg/Kg, Ã um Ãlcool sesquiterpÃnico comumente obtido de Matricaria chamomilla e de espÃcies do gÃnero (Vanillosmopsis), foi testado no modelo de lesÃo gÃstrica induzida por etanol para a investigaÃÃo microscÃpica do efeito gastroprotetor dessa droga, da influÃncia da migraÃÃo de neutrÃfilos neste efeito, assim como envolvimento das enzimas SuperÃxido dismutase (SOD) e Catalase (Cat). Foram quantificadas tambÃm a peroxidaÃÃo lipÃdica (Substancias Reativas ao Ãcido TiobarbitÃrico-TBARS), e o produto do metabolismo do Ãxido nÃtrico (NO), o Ãnion nitrito. O (-)-α-bisabolol foi capaz de diminuir o dano gÃstrico induzido pelo etanol, parÃmetro analisado microscopicamente. O (-)-α-bisabolol diminuiu a migraÃÃo de neutrÃfilos na mucosa gÃstrica em modelo de Ãlcera induzida por etanol absoluto em camundongos, quantificado atravÃs da enzima mieloperoxidase (MPO), presente nos neutrÃfilos. O (-)-α-bisabolol interagiu com o sistema enzimÃtico anti-oxidante diminuindo a atividade da enzima catalase na mucosa gÃstrica, nos animais tratados com etanol absoluto, diminuiu a peroxidaÃÃo lipÃdica (TBARS) no tecido gÃstrico em animais submetidos a aplicaÃÃo de etanol absoluto e foi capaz de aumentar a atividade da enzima superÃxido dismutase no mesmo tecido. O (-)-α-bisabolol nÃo alterou significativamente a quantidade de nitrito no estÃmago dos animais ulcerados. Desta forma, o (-)-α-bisabolol nas doses testadas reduz as lesÃes gÃstrica associadas a administraÃÃo de etanol, provavelmente pela reduÃÃo do estresse oxidativo no estomago, alÃm de reduzir a atividade da MPO, contudo se explica a aÃÃo gastroprotetora dessa droga, no entanto a reduÃÃo da atividade enzimÃtica da Catalase seria um achado menos importante para explicar a atividade antiulcerogÃnica verificada. / The (-)-α-bisabolol, at doses of 100 and 200 mg / kg, is an alcohol commonly obtained from Matricaria chamomilla and species of the genus (Vanillosmopsis), it was tested in ethanol-induced gastric injury model for research gastroprotective effect microscopically of this drug, the influence of neutrophil migration in this effect, as well as THE involvement of superoxide dismutase (SOD) and catalase (Cat) enzymes. It was also quantified the lipid peroxidation (Thiobarbituric Acid Reactive Substances-TBARS), and the nitric oxide metabolism product (NO), the anion nitrite. The (-)-α-bisabolol was able to decrease ethanol-induced gastric damage, parameter microscopically analyzed. The (-)-α-bisabolol decreased neutrophils migration to the gastric mucosa in absolute ethanol-induced ulcer model in mice, quantified by the myeloperoxidase enzyme (MPO), present in neutrophils. The (-)-α-bisabolol interacted with the anti-oxidant enzyme system decreasing the catalase enzyme activity in the gastric mucosa in animals treated with absolut ethanol, decreased lipid peroxidation (TBARS) in gastric tissue in rats exposed to ethanol and it was able to increase the superoxide dismutase activity in the same tissue. The (-)-α-bisabolol did not significantly alter the amount of nitrite in the ulcerated animals stomach. Thus, the (-)-α-bisabolol in the doses tested reduced the gastric lesions associated with administration of ethanol, probably by reducing oxidative stress in the stomach while reducing the activity of MPO, it being explained the gastroprotective action of this drug, however the reduction of enzymatic activity of Catalase would be a less important finding to explain the antiulcer activity observed it.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Objective: To evaluate the protective effect of the heme-oxygenase 1 (HO-1)/biliverdin/CO pathway in models of gastropathy in mice, evaluating the role of the soluble guanylate cyclase (GCs) and of the constitutive NOS in this event. Methods: Protocol 1: Mice were pre-treated with hemin (HO-1 inducer; 1,3,10 mg/Kg, i.p.), biliverdin (HO-1 product; 1,3 or 10 mg/Kg., i.p.), DMDC (CO donor; 2.5, 7.5, 12.5 or 10 Âmol/Kg, i.p.) or ZnPP IX (HO-1 antagonist; 0,3, 1 or 3 mg/kg. i.p.), one hour before, gastric damage was induced by ethanol 50% (hemin, biliverdin, DMDC) or 25% (ZnPP IX). In another group, the animals were pre-treated with ODQ (12.5 mg/kg, v.o) or L-NAME (3 mg/Kg, v.o), thirty minutes before of the treatments cited previously. After 1h, the mice were sacrificed and the stomachs removed for evaluation of the gastric lesions (Image J). Protocol 2: Mice were pre-treated with hemin (3 mg/Kg, i.p.), biliverdin (3 mg/Kg., i.p.), DMDC (12,5 Âmol/Kg) or ZnPP IX (3,0 mg/kg), one hour before of the administration of INDO 30 mg/Kg (hemin, biliverdin, DMDC) or 10 mg/Kg (ZnPP IX). In another group, the animals were pre-treated with ODQ (12.5 mg/kg, v.o) or L-NAME (3 mg/Kg, v.o), thirty minutes before of the treatments cited previously. Three hours after, the mice were sacrificed and the stomachs removed for evaluation of the gastric lesions, utilizing a digital paquimetry. In all of the experimental groups, fragments of the gastric mucous were collected for determination of the concentration of MDA, GSH or bilirubin. Another samples of tissue was removed for microscopic analyzes and HO-1 expression by immunohistochemistry. The detection of the TNF-α, IL-1β, IL-10 and MPO activity were evaluated only in the INDO gastropathy. Results: Ethanol increased the expression of HO-1 and the levels of bilirrubin in the gastric tissue. Hemin, biliverdin and DMDC reduced gastric damage, MDA levels and GSH consume in ethanol 50%- induced gastropathy. The histological parameters, edema, hemorrhage and loses of epithelial cells, were diminished in the presence of hemin, biliverdin or DMDC. ZnPP IX amplified the ethanol-induced gastric lesion, increased MDA formation and decreased the GSH concentration in gastric mucosa. The histological parameters also were amplified after the handling with ZnPP IX. Bilirubin concentration was elevated during the protection induced by hemin and biliverdin, but not DMDC. INDO increased the HO-1 expression and the bilirrubin levels in the gastric mucosa. Hemin, biliverdin or DMDC reduced the gastric lesion, the MPO activity, and the MDA levels and increased the GSH concentration in the gastropathy INDO- induced. The histological parameters, edema, hemorrhage, loss of epithelial cells and the presence of inflammatory cells, were inhibited by hemin, biliverdin or DMDC. ZnPP IX amplified the effect of the INDO increasing the gastric lesion, the MPO activity, the MDA levels and the GSH consume. The histological parameters also were amplified after the handling with ZnPP IX. Bilirubin was shown elevated during the protection induced by hemin and biliverdin, but not DMDC. Hemin, biliverdin and DMDC diminished the TNF-α and IL-1β concentrations and increased the IL-10. ODQ and L-NAME completely abolished the DMDC protective gastric effect, but not biliverdin in the gastropathy ethanol or INDO- induced. Conclusion: HO-1/biliverdin/CO pathway plays a protective effect against ethanol or INDO-induced gastric damage. In the gastropathy by ethanol, the protection is dependent of the anti-oxidant action by bilirubin and CO. However, in the model of INDO gastropathy, we observe an anti-oxidant and anti-inflammatory action. The mechanism of gastro protective action of the CO, but not of the biliverdin, is dependent of the CO/ NOS/ GMPc pathway. / Objetivo: Avaliar o efeito protetor da via hemeoxigenase 1 (HO-1)/ biliverdina/ CO em modelos de gastropatia em camundongos e o papel da guanilato ciclase solÃvel (GCs) e da NOS constitutiva neste evento. MÃtodos: Protocolo 1: Camundongos foram prÃ-tratados hemina (indutor da HO-1; 1,3 ou 10mg/Kg, i.p.), biliverdina (produto da HO-1; 1,3 ou 10mg/Kg, i.p.), DMDC (doador de CO; 2,5, 7,5, 12,5 ou 25 μmol/Kg, i.p.) ou ZnPP I(inibidor da HO-1; 0,3, 1,0 ou 3,0 mg/kg. i.p.) uma hora antes da administraÃÃo por gavagem de etanol 50% (hemina, biliverdina, DMDC) ou 25% (ZnPP IX). Em outro grupo, os animais foram prÃ-tratados com ODQ (12,5 mg/kg, v.o) ou L-NAME (3 mg/Kg, v.o), trinta minutos antes dos tratamentos citados anteriormente. Depois de 1h, os camundongos foram sacrificados e os estÃmagos removidos para avaliaÃÃo das lesÃes gÃstricas (Image J). Protocolo 2: Camundongos foram prÃ-tratados hemina (3,0 mg/kg), biliverdina (3,0 mg/kg), DMDC (12,5 μmol/Kg) ou ZnPPIX (3,0 mg/Kg) uma hora antes da administraÃÃo de INDO 30 mg/Kg (hemina, biliverdina, DMDC) ou 10 mg/Kg (ZnPP IX). Em outro grupo os animais foram prÃ-tratados com ODQ (12,5 mg/kg, v.o) ou L-NAME (3 mg/Kg, v.o), trinta minutos antes dos tratamentos citados anteriormente. TrÃs horas depois, os camundongos foram sacrificados e os estÃmagos removidos para avaliaÃÃo das lesÃes gÃstrica, utilizando um paquÃmetro digital. Em todos os grupos experimentais, fragmentos da mucosa gÃstrica foram coletados para determinaÃÃo da concentraÃÃo de MDA, GSH e bilirrubina. Outra amostra de tecido foi retirada para analise microscÃpica e imunohistoquÃmica. A detecÃÃo das citocinas TNF-α, IL-1β e IL-10, bem como a atividade de MPO foram avaliados somente na gastropatia por INDO. Resultados: O etanol aumentou a expressÃo de enzima HO-1 e dos nÃveis de bilirrubina no tecido gÃstrico. Hemina, biliverdina ou DMDC reduziram a lesÃo gÃstrica, os nÃveis de MDA e o consumo de GSH induzido por etanol 50%. Os parÃmetros histolÃgicos, edema, hemorragia e perda de cÃlulas epiteliais, foram diminuÃdos na presenÃa de hemina, biliverdina ou DMDC. ZnPP IX amplificou o efeito do etanol 25%, aumentando a lesÃo gÃstrica, os nÃveis de MDA e o consumo de GSH. Os parÃmetros histolÃgicos tambÃm foram amplificados apÃs o tratamento com ZnPP IX. A concentraÃÃo de bilirrubina se mostrou elevada apenas na gastroproteÃÃo induzida por hemina e biliverdina, mas nÃo pelo DMDC. INDO aumentou a expressÃo da HO-1 e os nÃveis de bilirrubina na mucosa gÃstrica. Hemina, biliverdina ou DMDC reduziram a lesÃo gÃstrica, a atividade de MPO, os nÃveis de MDA e aumentaram a concentraÃÃo de GSH na gastropatia por INDO. Os parÃmetros histolÃgicos, edema, hemorragia, perda de cÃlulas epiteliais e a presenÃa de cÃlulas inflamatÃrias, foram inibidas pela hemina, biliverdina ou DMDC. ZnPP IX amplificou o efeito da INDO aumentando a lesÃo gÃstrica, a atividade de MPO, os nÃveis de MDA e o consumo de GSH. Os parÃmetros histolÃgicos tambÃm foram amplificados apÃs o tratamento com ZnPP IX. Bilirrubina se mostrou elevada apenas na gastroproteÃÃo induzida por hemina e biliverdina, mas nÃo pelo DMDC. Hemina, biliverdina e DMDC diminuÃram as concentraÃÃes de TNF-α e IL-1β e aumentaram a IL-10. ODQ e L-NAME reverteram o efeito protetor do DMDC, mas nÃo da biliverdina, na gastropatia induzida por etanol ou INDO. ConclusÃo: A via HO-1/biliverdina/CO participa do processo de defesa da mucosa gÃstrica contra lesÃes induzidas por etanol ou INDO. Na gastropatia por etanol, a proteÃÃo à dependente da aÃÃo antioxidante da bilirrubina e CO. Entretanto, no modelo de gastropatia por INDO, observamos uma aÃÃo antioxidante e antiinflamatÃria. Evidenciamos ainda que o mecanismo de aÃÃo gastroprotetor do CO, mas nÃo da biliverdina à dependente da via CO/GMPc/NOS.

Orientador: Valdemiro Carlos Sgarbieri / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-04T13:50:25Z (GMT). No. of bitstreams: 1 Mezzaroba_LeoniceFatimaHoger_M.pdf: 1147865 bytes, checksum: 8e30210b748cf78769bb1bcfbba59462 (MD5) Previous issue date: 2005 / Resumo: A a-lactalbumina tem sido recentemente associada com redução de estresse, imunomodulação, atividade antimicrobiana após proteólise, propriedade anticancer e atividade antiulcerogênica. Os objetivos deste trabalho foram definir uma metodologia para a obtenção da a-lactalbumina e da b-lactoglobulina a partir de um concentrado de proteínas de soro de leite bovino e investigar a atividade antiulcerogênica da a-lactalbumina (produzida em laboratório e uma preparação comercial), da a-lactalbumina comercial hidrolisada e duas frações de seu hidrolisado (F1 < 1kDa e F2 > 1kDa) na proteção da mucosa gástrica em modelos de úlcera induzida por indomentacina e etanol absoluto em ratos, bem como, avançar na investigação das vias metabólicas de ação protetora. Para o isolamento da a-lactalbumina e da b-lactoglobulina a partir do concentrado de soro de leite bovino utilizou-se o sistema FPLC da Pharmacia e coluna de troca aniônica (resina Q Sepharose fast flow), e a fração correspondente a a- lactalbumina foi em seguida purificada por exclusão molecular utilizando-se a resina Sephacryl S-200. A b-lactoglobulina foi facilmente isolada por cromatografia de troca iônica apresentando-se quase homogênea e com um rendimento de 82%; para a a-lactalbumina, foi necessária uma etapa de purificação, e a proteína semi purificada apresentou contaminantes e baixo rendimento (32%). Para avaliar a ação antiulcerogênica da a-lactalbumina e de seus hidrolisados em modelo de úlcera induzido por indomentacina ou por etanol absoluto os animais receberam duas doses das amostras teste em dias consecutivos. Para avaliar possíveis vias de ação protetora foram estudadas suas participações na secreção ácida gástrica através da ligadura do piloro, a participação de substâncias sulfidrila e prostaglandinas na citoproteção gástrica em modelos de úlcera induzida por etanol absoluto. A a-lactalbumina comercial (Davisco Foods International, INC.) foi à amostra que apresentou maior porcentagem de inibição do índice de lesões ulcerativas no modelo de úlcera induzida por indometacina. No modelo de úlcera induzida por etanol absoluto, a a-lactalbumina (produzida em laboratório e a comercial) e frações de seu hidrolisado (F1 e F2) inibiram as lesões gástricas em níveis significativos na mesma ordem. A investigação das vias metabólicas de ação protetora, mostrarram que as amostras não alteraram a concentração ácida total após 4 horas de piloro ligado, sugerindo que a atividade antiulcerogênica desta proteína parece não ser mediada pela via da secreção ácida gástrica. A alquilação de grupamentos sulfidrila, envolvidos no mecanismo de citoproteção gástrica com N-etilmaleimida (NEM), eliminou o efeito protetor da a-lactalbumina e de frações de seu hidrolisado à mucosa gástrica, sugerindo que a ação antiulcerogênica parece depender da participação destas substâncias. A inibição da síntese de prostaglandina pela indometacina, bloqueador da síntese de prostaglandinas pela inibição da ciclooxigenase, não impediu que a a-lactalbumina (produzida em laboratório e a comercial) e a fração do hidrolisado de peso molecular >1kDa protejesse a mucosa gástrica a níveis significativos, sugerindo uma menor dependência de prostaglandina para a ação protetora dessas amostras. Já a fração do hidrolisado de peso molecular <1kDa perdeu sua atividade, evidenciando a participação de prostaglandinas na citoproteção gástrica por esta fração peptídica. A confirmação do envolvimento de prostaglandinas no mecanismo de ação antiulcerogênica por peptídios derivados da a-lactalbumina foi realizada através da quantificação do muco gástrico e da determinação da concentração de PGE2 na mucosa gástrica. Os resultados obtidos sugerem que há um conjunto de mecanismos envolvidos na proteção exercida pela a- lactalbumina e frações de seu hidrolisado enzimático sobre a mucosa gástrica, sendo estes, a participação de substâncias sulfidrila e aumento dos níveis de prostaglandina E2 na mucosa gástrica / Abstract: The a-lactalbumin has been recently associated with reduction of stress, immunomodulation, antimicrobial activity after proteolysis, anticancer and antiulcerogenic activity. The purpose of this work was to define a methodology for obtaing a-lactalbumin and b-lactoglobulin from a bovine whey protein concentrate and to investigate the antiulcerogenic activity of the a-lactalbumin (produced in laboratory and a commercial preparation ¿ Davisco Foods International, INC.), of the hidrolyzed commercial a-lactalbumin and two fractions of this hidrolysate (F1<1kDa and F2 >1kDa), in the protection of gastric mucosa induced by indomethacin or absolute ethanol induced ulcer in rats, as well as, to advance in the inquiry of the metabolic pathways of protective actions. For the isolation of the a-lactalbumin and of b-lactoglobulin from the bovine whey protein concentrate a Pharmacia FPLC system with anion exchange column (Q-Sepharose fast flow resin) was used. Alpha-lactalbumin was further purified by molecular exclusion chromatography using Sephacryl S-200 column. The b-lactoglobulin was easily isolated from ionic exchange chromatography presenting good purity and 82% yield; for the a-lactalbumin, a second stage of purification was necessary, and the partially purified protein still presented some contaminants and a low yield (35%). To evaluate the antiulcerogenic action of the a-lactalbumin and its hidrolysates for indomethacin and absolute ethanol induced ulcer in rats, the animals received two doses of the samples in consecutive days. To determine possible mechanisms of protection to the gastric mucosa, the effect in the gastric acid secretion through the tied piloro technique, the participation of sulfhydryl substances and prostaglandins were studied. For the indomethacin induced ulcer only the commercial a- lactalbumin inhibited the gastric injuries, while in the absolute ethanol induced ulcer all the samples were able to reduce the gastric injuries at significant levels. The inquiry of the metabolic pathways of protective action showed that the samples did not modify the concentration of the total acid after 4 hours tied piloro, suggesting that the antiulcerogenic activity of these proteins and peptides seem not to be mediated by the mechanism of gastric acid secretion. The alkylation of sulfhydryl groups with N-ethylmaleimide (NEM), partially eliminate the protective effect of the a-lactalbumin and its hidrolysates on the gastric mucosa, suggesting the participation of these groups in the antiulcerogenic action. The inhibition of the prostaglandin synthesis with indomethacin did not eliminate the protection offered by a-lactalbumin and the hydrolysate fraction of molecular weight > 1kDa. However the protection offered by the hydrolysate fraction of molecular weight < 1kDa was completely neutralysed by the indomethacin cycloxygenase inhibition, suggesting that a-lactalbumin low peptides seem to protect the gastric mucosa via the prostaglandin cycle. The confirmation of the envolvement of prostaglandins in the mechanism of antiulcerogenic action by a-lactalbumin peptides was substanciated through the quantification of gastric mucus and the determination of the PGE2 concentration in the gastric mucosa. These results suggest that there are more than one mechanism for the stomach cytoprotection against ulcerogenic factors a-lactalbumin and its hydrolysates. While intact a-lactalbumin and high molecular weight peptides seem to depend on the sulfhydryl groups for protection, low molecular weight peptides (MW < 1kDa) seem to act by stimulation of prostaglandin synthesis / Mestrado / Mestre em Alimentos e Nutrição

No description available.

Introduction The prognosis in oesophago-gastric cancer is poor with less than 15% patients surviving beyond 5 years after diagnosis. The addition of neoadjuvant therapy has been shown to increase survival in patients suitable for curative surgery. However, the additional gains are modest and the majority of patients do not respond sufficiently from therapy to gain any benefit. There is an urgent need to identify markers that can predict response to neoadjuvant therapy in order provide safer, more effective, individualised treatment regimes. Methods A prospective, multi-centre, collaborative study was undertaken in patients with oesophago-gastric cancer undergoing neoadjuvant therapy and potentially curative surgery. Levels of circulating biomarkers M2-Pyruvate kinase, alkaline phosphatase, CA19-9, CEA and CA 72-4 were measured in patients before and after administering the first cycle of chemotherapy. Binary logistic regression analysis was performed to assess the ability of biomarkers to predict histological response to therapy. Results 165 patients were recruited to the main study. 105 patients had complete histopathological data for analysis. There were 27 responders and 78 non-responders to neoadjuvant therapy. There were no differences in pre-therapy demographic, pathological or treatment factors between the two groups. Responders had less post-operative lymphovascular invasion (P= 0.004) and higher R0 resection rates (P=0.03). Pre-therapy M2-Pyruvate kinase levels were lower in responders compared to non-responders (P=0.037) and levels were able to predict response with each unit increase in the biomarker level being associated with a 4.1% decrease in the likelihood of response (P=0.027). M2-PK levels were not associated with any pre-operative demographic, clinical or pathological factors. Conclusions Pre-therapy dimeric M2-PK levels can predict response to neoadjuvant therapy in patients with oesophago-gastric cancer. The test could be of clinical value for 1 in every 8 patients undergoing the test.

In recent years, obesity has literally reached epidemic proportions throughout the world. Gastric electrical stimulation is a recent technique that uses an implanted device to stimulate the stomach and produce a feeling of satiety for overweight and obese patients. However, to place the implant, the patient currently needs to undergo an invasive surgical procedure. Endoscopic implantation could be used to place the gastric stimulator in the stomach. This would help moderately and morbidly obese patients that are ineligible for surgery, but such a solution brings new challenges for the development of the gastrostimulator. This thesis is a first step toward a commercial implant, endoscopically implantable and treating obesity. This work mainly focuses on the design and implementation of a first endoscopically implantable prototype, to be validated on animals. This will allow us to prove the feasibility of the project, through a pre-clinical phase on animals. Compared to previous devices, the prototype developed is specifically designed to stimulate the stomach using embedded electrodes. Its design allows endoscopic implantation. Its packaging resists long-term implantation in an acidic environment, hence overcoming the shortcomings of previous gastrostimulators. A flexible and low-cost manufacturing chain is implemented. The prototype is built with discrete components, commercially available, and encapsulated with silicone rubber. This thesis also provides a method to select a silicone rubber for the encapsulation of an electronics circuit. The validation of the prototype is performed on a bench-test, in ex-vivo and in-vivo on three dogs. A new method using surface cutaneous electrodes is introduced to validate the functioning of the stimulator. / Doctorat en Sciences de l'ingénieur et technologie / info:eu-repo/semantics/nonPublished

Bakgrund: Ett av mänsklighetens största hälsoproblem är övervikt och fetma. Ett högt BMI ökar risken för morbiditet och mortalitet, därför är en förändrad livsstil med bra matvanor och regelbunden motion det bästa alternativet för att gå ned i vikt. Viktreducerande kirurgi kan vara ett alternativ, som bör undersökas vidare. Syfte: Syftet med litteraturöversikten är att belysa hur hälsa och välmående påverkas hos personer som genomgått ett gastric bypass ingrepp. Metod: En litteraturöversikt utfördes för att studera valt problemområde. Femton vetenskapliga artiklar har använts. Kvalitetsgranskning av artiklarna har gjorts med hjälp av relevanta granskningsmallar och analysförfarandet utfördes av författarna tillsammans. Resultat: Livskvaliteten är lägre hos patienter som vill genomgå viktreducerande kirurgi än genomsnitts befolkning. Patienterna kände att de fick en andra chans i livet efter kirurgin, de uttryckte glädje, såg nya möjligheter och hade bättre välmående både psykiskt och fysiskt efter ingreppet. Det är vanligt med överskottshud, speciellt på magen som en följd av kraftig viktreducering. Patienterna kände frustration över nutritionen, då kosten inte var lika naturlig som tidigare. Det krävdes större måltidsplanering för att få ett tillräckligt näringsintag efter kirurgin. Diskussion: Majoriteten av deltagarnas livskvalitet höjdes och patienterna medverkade i fler sociala aktiviteter efter kirurgin. Patienterna skämdes dock över sin kropp efter kirurgin på grund av överskottshuden. Slutsats: Generellt ökade hälsan och välmående hos de personer som genomgått en viktminskningsoperation, de hade lättare att anpassa sig till samhället och kände sig inte längre överviktiga. / <p>Godkännande datum: 2016-10-31</p>

Background: Obesity has exploaded in the last decades and an ongoing increase is to be seen. The disease is rated as a huge epidemia of times and has developed to an economic social problem. Today more people die from obesity and it´s complications than from nutritional diseases and malnutrition. Gastric Bypass has proved to enable a new life including an improved health and quality of life but has also been critized for being a quick solution not resulting in a long term perspective weight loss. Aim: The aim of this study was to describe people´s experiences from going through Gastric Bypass surgery. Method: The method used was a literature study based on qualitative research. The articles were analysed according to Fribergs five step model and resulted in three main themes and nine sub-themes. Results: The main themes were- The last way out, The battle against oneself and On a new adventure. In order to be able to support these people keeping their new life style and weight reduction the nurse must have insight in people´s experiences of having undergone a Gastric Bypass surgery. Conclusion: The result showed that Gastric Bypass can be a last alternative for hope about a better future and a chance to an improved health and quality of life. Though the surgery has to be combined with individually created coping strategies and a genuine, strong will to make a change in order to become a successful action in a long term perspective.

No description available.

PDase II activity was determined using a synthetic substrate, the 2,4-dinitrophenyl ester of thymidine 3'-phosphate. The enzyme activity was estimated in fractions obtained by differential centrifugation of homogenates of epithelial cells fromt.the small intestinal mucosa of guinea pigs and rats. In guinea pig preparations PDase II occurred with highest specific activity in those fractions rich in succinate dehydrogenase and acid phosphatase. A lysosomal location for the guinea pig enzyme was indicated by its structure-linked latency and by its association with particles which underwent a characteristic decrease in equilibrium density when Triton WR-1339 was injected into the animals. With rat preparations a much greater proportion of the PDase II activity was found in the soluble fraction after uult-ra;c;entrifugation. The rat enzyme exhibited a lower degree of latency and administration of Triton WR-1339 had no effect. The rat enzyme activity in these crude preparations further differed from that of the guinea pig in other respects; it was more labile at 60°C, exhibited a slightly lower pH optimum, had a higher molecular weight as determined by gel filtration chromatography and displayed a much smaller tendency to aggregate under Llow salt conditions. Both enzymes were purified by chromatography on DEAE-cellulose, CM-cellulose and agarose, the extensive purification (550 fold) of the rat enzyme being largely due to its behaviour oh the latter material where it was found to bind tenaciously in low ionic strength solutions. On the other hand, only a fifteen-fold purification of the guinea pig enzyme was obtained because of its tendency tofform insoluble aggregatesdduring the chromatographic steps. In the main, the properties of the partially purified enzymes were quite similar. Both displayed pH optima between pH 6 and 7, were inhibited in solutions of high ionic strength, were unaffected' by divalent cations or EDTA, were similarly inactivated by heating at a temperature of 60°G displayed discontinuous Arrhenius plots _5 and exhibited Km values of the order 2-5x10 M for dTpDNP. In most casestfche differences between the enzymes were just differences of degree and could probably be accounted for byethe different extents to which the enzymes were purified. A more extensive characterization of the highly purified rat PDase was carried out. The fall-off in PDase II reaction rate observed at high enzyme levels with dTpDNP as substrate was found to be due to competitive inhibition of the enzyme by dTp, a reaction product which showed a of 2x10 M. The isoelectric point of PDase II was estimated by electrofocusing but since multiple peaks of activity were found at pH 3.4, 4.2-4.5, and pH 7.2 a conclusive result was not obtained. Polyacrylamide gel electrophoresis of purified rat PDase II indicated that the pattern obtained was, in part, dependent on whether the preparation was fresh or not; freshly purified PDase II contained up to 10 bands in gels stained for protein whereas only 1-2 bands were obtained when the preparations were "aged". A molecular weight of 150000-170000 for the enzyme was estimated in experiments performed by gel-filtration chromatography on dextran and agarose gels. Investigation of the interaction with, and hydrolysis by, rat PDase II of a number of possible phosphodiester substrates indicated that'-, the enzyme required a nucleoside 3'-phosphoryl residue for the initiation of hydrolysis which then proceeded in a 5'+3' direction. Finally, the effect of some enzyme inhibitors was investigated. PDase II activity was inhibited in the presence; of NEM, PCMB, PCMPS and iodoacetic acid. It was further found that the inactivation by iodoacetic acid could be prevented by the presence of a PDase substrate or, better still, by dTp. This is good evidence that iodoacetate alkylates an essential residue at the active center of PDase II and is the first time that such an effect has been shown for a PDase. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate