Thesis (Ph.D.) -- University of Adelaide, Department of Animal Science, 1992.

Includes bibliographical references (leaves 159-213) Shows that IGF-I peptides are effective in diminishing post-surgical catabolism and enhancing adaptive gut hyperplasia in rats recovering from massive small bowel resection.

xxiii, 222 leaves : ill., plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Shows that IGF-I peptides are effective in diminishing post-surgical catabolism and enhancing adaptive gut hyperplasia in rats recovering from massive small bowel resection. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Science, 1992

Estudos com farinha de banana verde (FBV), rica em amido resistente, mostram efeitos positivos sobre a saciedade, resposta glicêmica e melhora do funcionamento intestinal. Entretanto, pouco se sabe sobre a capacidade da FBV em estimular seletivamente o crescimento e/ou atividades de microbiota intestinal benéfica e os efeitos fisiológicos do consumo habitual. No presente trabalho foi investigado o efeito da ingestão regular e descontinuada de FBV sobre a microbiota intestinal em voluntários saudáveis, bem como as interações com hormônios relacionados à fome e saciedade, funcionamento intestinal e homeostase da glicose. Para tanto foi realizado estudo de intervenção, duplo cego paralelo controlado com placebo, no qual voluntários saudáveis consumiram FBV ou maltodextrina, veiculadas através de sopa prontas congeladas, três vezes por semana e durante seis semanas. Os resultados evidenciaram que a FBV pode aumentar a saciedade, promover redução no aporte energético de refeições subsequentes (14%) e melhorar o funcionamento intestinal. Ao mesmo tempo reduz a secreção plasmática de insulina no jejum e o Índice HOMA2-RI em 20%, sinalizando aumento na sensibilidade à insulina. A análise da microbiota intestinal utilizando o rDNA 16S mostrou que existem dois grupos distintos de indivíduos, os quais respondem diferentemente ao consumo de FBV. O consumo de FBV por voluntários, cujo microbioma era mais abundante no gênero Prevotella, apresentou aumento de genes envolvidos em vias metabólicas relacionadas à degradação anaeróbia de carboidratos (794 Kegg orthologs, FDR=0,05), como as vias do metabolismo de amido e glicose, do butirato, propionato. Paralelamente outros genes indicaram redução de algumas vias metabólicas, incluindo a biossíntese de lipopolissacarídeos. Este mesmo grupo de voluntários apresentou gêneros microbianos positivamente relacionados com conteúdo de ácidos graxos de cadeia curta (AGCC), em padrão distinto do outro grupo de voluntários que consumiu FBV e do grupo Controle. Foi possível demonstrar que o consumo de FBV pode promover a modulação do microbioma em indivíduos saudáveis com enterótipos distintos, trazendo efeitos benéficos para a saúde humana. / Studies with Unripe Banana Flour, rich in resistant starch, shave shown positive effects on satiety, glycemic response and improved intestinal function. Nevertheless, little is known about its capacity to selectively stimulate the intestinal microbiota\'s activity, or the physiological effects of its habitual consumption. This study investigated the effects of the regular, discontinued ingestion of UBF on the intestinal microbiome in healthy volunteers, as well as effects on hormones related to satiety, intestinal function and glucose homeostasis. To achieve these goals, a double blind, parallel, placebo controlled study was designed, in which healthy volunteers ingested UBF or maltodextrin added to a standardized frozen soup meal, 3 times a week for 6 weeks. The results showed that UBF can improve satiety, promote a reduction in energy intake at subsequent meals (14%) and improve intestinal function. At the same time, it reduces plasmatic secretion of fasting insulin and e the HOMA2-RI index by 20%, signaling an increase in insulin sensitivity. The analysis of the microbiome using the 16S rDNA gene showed that there are two clusters of individuals, which respond differently to the dietary intervention. The UBF consumption by volunteers with a Prevotella dominant microbiome showed an increase in genes related to anaerobic carbohydrate degradation (794 Kegg orthologs, FDR=0,05), such as members of the starch and glucose metabolism, propanoate metabolism and butyrate metabolism. At the same time, other genes were reduced, including the biosynthesis of lipopolysaccharides. The same volunteers presented several microbial groups positively correlated with the short chain fatty acids (SCFA) present in the fecal samples analyzed. This was a distinct pattern to that observed for the remaining volunteers. We demonstrated that the consumption of UBF can promote the overall health of the human host as well as the modulation of the intestinal microbiome in healthy individuals and that this effect is dependent on the enterotype present.

Η χολοπαγκρεατική εκτροπή αποτελεί την πιο αποτελεσματική μέθοδο της βαριατρικής χειρουργικής όσο αφορά την απώλεια του βάρους και την υποχώρηση του σακχαρώδους διαβήτη τύπου 2, συνοδεύεται όμως συχνά από σημαντική έλλειψη θρεπτικών συστατικών. Η επιμήκης γαστρεκτομή είναι μια σχετικά νέα επέμβαση, η οποία σύμφωνα με μελέτες προκαλεί σημαντικού βαθμού απώλεια βάρους και υποχώρηση του σακχαρώδους διαβήτη τύπου 2. Σκοπός: Η προοπτική εκτίμηση και σύγκριση της επίδρασης της χολοπαγκρεατικής εκτροπής μακρών ελίκων και της λαπαροσκοπικής επιμήκους γαστρεκτομής στην υποχώρηση του σακχαρώδους διαβήτη τύπου 2, της υπέρτασης και της δυσλιπιδαιμίας, καθώς επίσης και στα επίπεδα ινσουλίνης, γλυκαγόνης, γκρελίνης, PYY και GLP-1( σε νηστεία αλλά και μετά από τη λήψη γλυκόζης ) σε ασθενείς με κλινικά σοβαρή παχυσαρκία και σακχαρώδη διαβήτη τύπου2. Μέθοδος: Δώδεκα ασθενείς (ΔΜΣ 57.6±9.9 kg/m2) υποβλήθηκαν σε χολοπαγκρεατική εκτροπή μακρών ελίκων και δώδεκα (ΔΜΣ 43.7±2.1 kg/m2 ) σε λαπαροσκοπική επιμήκη γαστρεκτομή. Όλοι οι ασθενείς παρουσίαζαν σακχαρώδη διαβήτη τύπου 2 και μελετήθηκαν προεγχειρητικά και σε 1, 3 και 12 μήνες μετά το χειρουργείο. Σε όλους τους χρόνους υποβλήθηκαν σε από του στόματος δοκιμασία ανοχής γλυκόζης. Αποτελέσματα: Το σωματικό βάρος σημείωσε σημαντική και αναλόγου μεγέθους μείωση και στις δύο ομάδες (Ρ<0.001). Στους 12 μήνες η ποσοστιαία απώλεια του υπερβάλλοντος σωματικού βάρους ήταν παρόμοια στις δύο ομάδες (Ρ=0.8) και ο σακχαρώδης διαβήτης είχε υποχωρήσει σε όλους τους ασθενείς. Η γλυκόζη, η ινσουλίνη και η αντίσταση στη δράση της παρουσίαζαν σημαντική μείωση έπειτα και από τις δύο επεμβάσεις, όμως η ευαισθησία στην ινσουλίνη ενισχύθηκε περισσότερο έπειτα από τη χολοπαγκρεατική εκτροπή (Ρ=0.003). Η αρτηριακή πίεση, η ολική και η LDL χοληστερόλη μειώθηκαν σημαντικά έπειτα από τη χολοπαγκρεατική εκτροπή (Ρ<0.001), όχι όμως και μετά την επιμήκη γαστρεκτομή. Τα τριγλυκερίδια μειώθηκαν σημαντικά και στις δύο ομάδες, ενώ η HDL χοληστερόλη παρουσίασε σημαντική αύξηση μόνο μετά την επιμήκη γαστρεκτομή (Ρ<0.001). Τα επίπεδα γκρελίνης νηστείας δεν μεταβλήθηκαν σημαντικά μετά τη χολοπαγκρεατική εκτροπή (Ρ=0.2), ενώ σημείωσαν σημαντική μείωση μετά την επιμήκη γαστρεκτομή (Ρ<0.001). Η απόκριση των ΡΥΥ και GLP-1 ενισχύθηκε σημαντικά και στις δύο ομάδες ασθενών (Ρ=0.001). Συμπεράσματα: Η λαπαροσκοπική επιμήκης γαστρεκτομή οδήγησε σε αναλόγου βαθμού απώλεια σωματικού βάρους και υποχώρηση του σακχαρώδη διαβήτη τύπου 2 με τη χολοπαγκρεατική εκτροπή μακρών ελίκων. Η χολοπαγκρεατική εκτροπή όμως ήταν περισσότερο αποτελεσματική όσο αφορά τη βελτίωση της ευαισθησίας στην ινσουλίνη, της δυσλιπιδαιμίας και της αρτηριακής υπέρτασης. / Biliopancreatic diversion (BPD) is the most effective bariatric procedure in terms of weight loss and remission of diabetes type 2 (DM2) but it is accompanied by nutrient deficiencies. Sleeve gastrectomy (SG) is a relatively new restrictive operation that has shown promising results concerning DM2 resolution and weight loss. Objective: To evaluate and compare prospectively the effects of BPD long limb (BPDLL) and SG on remission of DM2, hypertension and dyslipidemia and also on fasting, and glucose-stimulated insulin, glucose, glucagon, ghrelin, PYY and glucagon-like peptide-1 (GLP-1) levels in morbidly obese patients with DM2. Methods: Twelve patients (BMI 57.6±9.9 kg/m2) underwent BPDLL and 12 (BMI 43.7±2.1 kg/m2) underwent SG. All patients had DM2 and were evaluated before and 1, 3 and 12 months after surgery. Oral glucose tolerance test and blood sampling were carried out after an overnight fast and 30, 60 and 120 minutes after glucose ingestion. Results: Body weight decreased markedly in both groups (P<0.001); excess weight loss was similar in both groups at 12 months (P=0.08) and DM2 resolved in all patients. Glucose, insulin and insulin resistance decreased significantly after both procedures, but the BPDLL group had higher insulin sensitivity than the SG group at 1 year (P=0.003). Blood pressure, total and LDL cholesterol decreased markedly after BPDLL (P<0.001) but not after SG. Triglycerides decreased significantly after both operations but HDL increased significantly after SG only (p<0.001). Fasting ghrelin did not change significantly after BPDLL (P=0.2), but decreased markedly after SG (P<0.001). Fasting GLP-1 and PYY increased significantly after BPDLL only (P=0.01), however GLP-1 and PYY responses to glucose were significantly enhanced in both groups (P=0.001). Conclusion: SG results in weight loss and resolution of DM2 comparable to BPDLL, but BPDLL is more effective in terms of dyslipidemia resolution and blood pressure reduction.

Indiana University-Purdue University Indianapolis (IUPUI) / Glucagon-like peptide 1 (GLP-1) receptor agonists are a class of incretin based therapeutics which aid in blood glucose management in Type II diabetes mellitus (T2DM). Recent studies have demonstrated direct cardiovascular benefits conferred by these agents including protection in ischemia and heart failure. Despite these observations, human clinical trials fail to support improvements in cardiovascular outcomes independent of glucose lowering effects in the T2DM populations. Prior data from our lab demonstrate that obesity impairs GLP-1 associated increases in myocardial glucose uptake. However, the reasons for this impairment/resistance to cardiac effects of GLP-1 in the setting of obesity remain ill defined. This investigation tested the hypothesis that underlying differences in the cardiac proteome and microRNA (miR) transcriptome could contribute to distinct cardiac responses to ischemia and activation of GLP-1 signaling in the setting of obesity. To identify whether obesity modulated cardiac functional responses to GLP 1 related drugs, we first examined the effects of obesity on cardiac function, miR transcriptome, and proteome in response to short duration ischemia-reperfusion (I/R). We observed divergent physiologic responses (e.g. increased diastolic volume and systolic pressure in lean, decreased diastolic volumes in obese) to regional I/R in obese vs lean hearts that were associated with significant molecular changes as detected by protein mass spectrometry and miR microarray. Molecular changes were related to myocardial calcium handling (SERCA2a, histidine-rich Ca2+ binding protein), myocardial structure and function (titin), and miRs relating to cardiac metabolism, hypertrophy, and cell death, including miR-15, miR-30, miR-199a, miR-214. Importantly, these effects were modified differently by GLP-1 agonism in lean vs obese swine. Additional studies investigated the functional effects of 30 days of treatment with the GLP-1 analogue liraglutide on a model of slowly-developing, unrelieved coronary ischemia. Liraglutide failed to reduce infarct size or collagen deposition. However, analysis of left ventricular pressure-volume relationships support that liraglutide improved diastolic relaxation/filling, load-dependent indices of cardiac function, and cardiac efficiency in response to sympathetic stimulation in obese swine. Taken together, these findings support that miR and proteomic differences underlie distinct changes in functional cardiac responses to I/R and pharmacologic activation of GLP-1 signaling in the setting of obesity.

A cada dia cresce o interesse por alimentos ricos em carboidratos não disponíveis em virtude da relação inversa entre seu consumo e o risco de doenças crônicas não transmissíveis (DCNT). No presente trabalho, foi avaliado o potencial fisiológico da farinha de banana verde (FBV) como ingrediente funcional. Em ratos adultos, foi realizado ensaio de média duração (28 dias) para avaliação do efeito trófico da FBV sobre o intestino grosso e de parâmetros relacionados à tolerância à glicose. Em humanos, foram realizados ensaios clínicos de curta e média duração para avaliação dos efeitos sobre resposta glicêmica; liberação de hormônios gastrintestinais relacionados à saciedade; status antioxidante; fome e saciedade; e funcionamento intestinal. A FBV foi produzida com banana verde, Musa acuminata, de acordo com patente depositada pelo grupo (Patente (RPI - 1941), 2008). A FBV é uma fonte concentrada de carboidratos não disponíveis, com 56% de AR e 8% de FAT na base integral. A adição de FBV nas rações provocou efeito trófico no ceco dos animais, evidenciado por aumento no índice metafásico, número de células da cripta e profundidade das criptas. Além disso, a ração com FBV proporcionou melhora nos parâmetros relacionados à tolerância à glicose. Em voluntários saudáveis, a ingestão de uma única refeição adicionada de 8 g de FBV proporcionou aumento na saciedade e boa correlação entre os parâmetros fome/saciedade e níveis plasmáticos de grelina e insulina, melhorou o funcionamento intestinal, além de resultar em alta fermentabilidade in vitro em relação à lactulose. Após ingestão diária da FBV por 14 dias, os resultados da ingestão de RC0 (refeição controle antes do tratamento) e de RC14 (RC0 após 14 dias de tratamento) mostraram que ocorre melhora na tolerância à glicose, evidenciada pela menor liberação de insulina durante o GTT. O efeito positivo sobre funcionamento intestinal, sobre saciedade e sobre liberação de hormônios gastrintestinais no plasma permaneceu após ingestão prolongada da FBV. A adição da FBV na refeição resultou em aumento da capacidade antioxidante in vitro. A FBV apresenta inúmeros atributos positivos para elaboração de produtos que ampliem as opções para uma alimentação saudável, bem como propiciem saúde intestinal, visando a diminuição do risco de DCNT. / The study of unavailable carbohydrates has been of great concern due to their inverse relation with the risk for non-transmissible chronic diseases (NTCD). In the present study, the functional potential of unripe banana flour (UBF) was evaluated. In rats, a medium-term assay was carried in order to evaluate parameters related to glucose tolerance and the trophic effect of UBF on the large bowel. In healthy volunteers, short and medium-term clinical assays were carried to evaluate the effects of UBF on glycemic response; release of gastrointestinal hormones related to satiety (ghrelin, leptin and insulin); antioxidant status; hunger and satiety; and intestinal health. UBF was produced with unripe banana, Musa acuminata, subgroup Cavendish, maturation stage I, in industrial scale and according to a patent deposited by the group (Patent (RPI - 1941), 2008). UBF is a concentrated source of unavailable carbohydrates, with 56% RS and 8% DF (wet weight). Adding UBF in rat rations resulted in a trophic effect in the animals\' cecum, which was evidenced by increase in the metaphasic index, number of crypt cells and crypt depth. Moreover, the ration with UBF resulted in better glucose tolerance parameters. In healthy volunteers, adding UBF (8 g) to an only meal provided significant satiety and good correlation between the parameters hunger/ satiety and plasmatic levels of ghrelin and insulin, improved bowel habit, as well as resulted in high in vitro fermentability in relation to lactulose. After daily intake of UBF for 14 days, the results of the intake of RC0 (control meal before treatment) and RC14 (RC0 after 14 days treatment) showed that there is a positive post-prandial variation in the plasmatic concentrations of gastrointestinal hormones, as well as improvement in glucose tolerance, evidenced by lower insulin release during GTT. The positive effect on bowel habit, satiety and release of gastrointestinal hormones in plasma was kept after prolonged intake of UBF. Adding UBF to the meal provided significant increase in the in vitro antioxidant capacity. UBF presents several positive attributes for the elaboration of products that may increase the options for healthy eating habits, as well as provide intestinal health, always aiming to decrease the risk for NTCD.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2016-06-02T12:58:47Z No. of bitstreams: 2 Dissertação - Marina Monteiro Celestino - 2016.pdf: 3038939 bytes, checksum: f658681fb77c19cdbec1ee83ee51b443 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-06-02T14:50:30Z (GMT) No. of bitstreams: 2 Dissertação - Marina Monteiro Celestino - 2016.pdf: 3038939 bytes, checksum: f658681fb77c19cdbec1ee83ee51b443 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2016-06-02T14:50:30Z (GMT). No. of bitstreams: 2 Dissertação - Marina Monteiro Celestino - 2016.pdf: 3038939 bytes, checksum: f658681fb77c19cdbec1ee83ee51b443 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2016-02-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Overweight and obesity are associated with excessive food intake, due to changes in the productions of gastrointestinal hormones productions. Objectives: To evaluated the effect of a herbal extract derived from native species of South America on food intake, acylated ghrelin concentrations and peptide similar to glucagon 1. Material and methods: A randomized, blind, placebo-controlled, crossover design methodology, with intervention in two days with an interval (washout) seven days, consisted of 20 overweight women. Three capsules a mix of herbal medicines were administered, containing 112 mg of yerba mate, guarana 95 mg and 36 mg of damiana, or three placebo capsules containing 100 mg of lactose. The herbal extract was administered 15 minutes before a standardized breakfast (494.50 kcal, carbohydrates 52.67%, 12.91% protein and 34.5% lipid) and a standard lunch (632.05 kcal, 61, 67% carbohydrates, 16.97% protein and 21.44% lipid) for all patients. Food not eaten by the participants was weighed to evaluated food intake. Blood samples were collected at baseline and on days 45, 60, 90, 150, 210 minutes after breakfast in the morning and lunch for determination of plasma glucose concentrations, acylated ghrelin and peptide similar to glucagon 1. To compare the differences of the mean energy food intake and macronutrient was performed paired t-test, for the behavior of hormones was performed ANOVA and was calculated area under the curve and to determine the differences between the areas was performed Student's t test. Results: In the supplemented group, there was significant reduction in energy intake at lunch and macronutrients in both meals (p <0.05). The acylated ghrelin concentrations were lower after breakfast (p <0.05) and glucagon-like peptide 1 were higher (p <0.05) after breakfast in the supplemented group. Conclusion: Supplementation with herbal mix reduced energy intake and macronutrients by the modulating hormones glucagon-like 1 and acylated ghrelin in overweight and obesity women. / O excesso de peso se relaciona com a ingestão alimentar excessiva, decorrente de alterações nas produções de hormônios gastrointestinais. Objetivos: Avaliar o efeito de um extrato de ervas oriundos de espécies nativas da América do Sul sobre a ingestão alimentar, as concentrações de grelina acilada e peptídeo semelhante ao glucagon 1. Material e métodos: Ensaio clínico randomizado cego, crossover com intervenção em dois dias, com intervalo (washout) de sete dias, composto por 20 mulheres adultas com excesso de peso. Foram administradas três cápsulas de um extrato de ervas, contendo 112 mg de erva-mate, 95 mg de guaraná e 36 mg de damiana, ou três cápsulas de placebo, contendo 100 mg de lactose. O extrato de ervas foi administrado 15 minutos antes de um desjejum padronizado (494,50 kcal, 52,67% carboidratos, 12,91% proteínas e 34,5% lipídios) e de um almoço padronizado (632,05 kcal, 61,67% carboidratos, 16,97% proteínas e 21,44% lipídios) para todas pacientes. Os alimentos não ingeridos pelos participantes foram pesados para avaliar a ingestão alimentar. Foram coletadas amostras de sangue no início do estudo e nos tempos de 45, 60, 90, 150, 210 minutos após o café-da-manhã e almoço para determinação das concentrações plasmáticas de glicose, grelina acilada e peptídeo semelhante ao glucagon 1. Para comparar as diferenças das médias da ingestão alimentar energética e de macronutrientes foi realizado o teste t pareado, para o comportamento dos hormônios foi realizado ANOVA e foi calculado a área abaixo da curva e para determinar as diferenças entre as áreas foi realizado teste T de Student. Resultados: No grupo suplementado, foi observada redução significativa da ingestão energética no almoço e de macronutrientes em ambas as refeições (p < 0,05). As concentrações de grelina acilada foram menores após o almoço (p <0,05) e de peptídeo semelhante ao glucagon 1 foram maiores (p < 0,05) após o desjejum no grupo suplementado. Conclusão: A administração do extrato de ervas reduziu a ingestão calórica e de macronutrientes sugerindo que possa ter ocorrido por meio da modulação da ação dos hormônios peptídeo semelhante ao glucagon 1 e grelina acilada em mulheres com sobrepeso e obesidade.

A cada dia cresce o interesse por alimentos ricos em carboidratos não disponíveis em virtude da relação inversa entre seu consumo e o risco de doenças crônicas não transmissíveis (DCNT). No presente trabalho, foi avaliado o potencial fisiológico da farinha de banana verde (FBV) como ingrediente funcional. Em ratos adultos, foi realizado ensaio de média duração (28 dias) para avaliação do efeito trófico da FBV sobre o intestino grosso e de parâmetros relacionados à tolerância à glicose. Em humanos, foram realizados ensaios clínicos de curta e média duração para avaliação dos efeitos sobre resposta glicêmica; liberação de hormônios gastrintestinais relacionados à saciedade; status antioxidante; fome e saciedade; e funcionamento intestinal. A FBV foi produzida com banana verde, Musa acuminata, de acordo com patente depositada pelo grupo (Patente (RPI - 1941), 2008). A FBV é uma fonte concentrada de carboidratos não disponíveis, com 56% de AR e 8% de FAT na base integral. A adição de FBV nas rações provocou efeito trófico no ceco dos animais, evidenciado por aumento no índice metafásico, número de células da cripta e profundidade das criptas. Além disso, a ração com FBV proporcionou melhora nos parâmetros relacionados à tolerância à glicose. Em voluntários saudáveis, a ingestão de uma única refeição adicionada de 8 g de FBV proporcionou aumento na saciedade e boa correlação entre os parâmetros fome/saciedade e níveis plasmáticos de grelina e insulina, melhorou o funcionamento intestinal, além de resultar em alta fermentabilidade in vitro em relação à lactulose. Após ingestão diária da FBV por 14 dias, os resultados da ingestão de RC0 (refeição controle antes do tratamento) e de RC14 (RC0 após 14 dias de tratamento) mostraram que ocorre melhora na tolerância à glicose, evidenciada pela menor liberação de insulina durante o GTT. O efeito positivo sobre funcionamento intestinal, sobre saciedade e sobre liberação de hormônios gastrintestinais no plasma permaneceu após ingestão prolongada da FBV. A adição da FBV na refeição resultou em aumento da capacidade antioxidante in vitro. A FBV apresenta inúmeros atributos positivos para elaboração de produtos que ampliem as opções para uma alimentação saudável, bem como propiciem saúde intestinal, visando a diminuição do risco de DCNT. / The study of unavailable carbohydrates has been of great concern due to their inverse relation with the risk for non-transmissible chronic diseases (NTCD). In the present study, the functional potential of unripe banana flour (UBF) was evaluated. In rats, a medium-term assay was carried in order to evaluate parameters related to glucose tolerance and the trophic effect of UBF on the large bowel. In healthy volunteers, short and medium-term clinical assays were carried to evaluate the effects of UBF on glycemic response; release of gastrointestinal hormones related to satiety (ghrelin, leptin and insulin); antioxidant status; hunger and satiety; and intestinal health. UBF was produced with unripe banana, Musa acuminata, subgroup Cavendish, maturation stage I, in industrial scale and according to a patent deposited by the group (Patent (RPI - 1941), 2008). UBF is a concentrated source of unavailable carbohydrates, with 56% RS and 8% DF (wet weight). Adding UBF in rat rations resulted in a trophic effect in the animals\' cecum, which was evidenced by increase in the metaphasic index, number of crypt cells and crypt depth. Moreover, the ration with UBF resulted in better glucose tolerance parameters. In healthy volunteers, adding UBF (8 g) to an only meal provided significant satiety and good correlation between the parameters hunger/ satiety and plasmatic levels of ghrelin and insulin, improved bowel habit, as well as resulted in high in vitro fermentability in relation to lactulose. After daily intake of UBF for 14 days, the results of the intake of RC0 (control meal before treatment) and RC14 (RC0 after 14 days treatment) showed that there is a positive post-prandial variation in the plasmatic concentrations of gastrointestinal hormones, as well as improvement in glucose tolerance, evidenced by lower insulin release during GTT. The positive effect on bowel habit, satiety and release of gastrointestinal hormones in plasma was kept after prolonged intake of UBF. Adding UBF to the meal provided significant increase in the in vitro antioxidant capacity. UBF presents several positive attributes for the elaboration of products that may increase the options for healthy eating habits, as well as provide intestinal health, always aiming to decrease the risk for NTCD.

Infiltration of myeloid cells in the tumor microenvironment is often associated with enhanced angiogenesis and tumor progression, resulting in poor prognosis in many types of cancer. The polypeptide chemokine PK2 (Bv8, PROK2) has been shown to regulate myeloid cell mobilization from the bone marrow, leading to activation of the angiogenic process, as well as accumulation of macrophages and neutrophils in the tumor site. Neutralizing antibodies against PK2 were shown to display potent anti-tumor efficacy, illustrating the potential of PK2-antagonists as therapeutic agents for the treatment of cancer. In this study we demonstrate the anti-tumor activity of a small molecule PK2 antagonist, PKRA7, in the context of glioblastoma and pancreatic cancer xenograft tumor models. For the highly vascularized glioblastoma, PKRA7 was associated with decreased blood vessel density and increased necrotic areas in the tumor mass. Consistent with the anti-angiogenic activity of PKRA7 in vivo, this compound effectively reduced PK2-induced microvascular endothelial cell branching in vitro. For the poorly vascularized pancreatic cancer, the primary anti-tumor effect of PKRA7 appears to be mediated by the blockage of myeloid cell migration/infiltration. At the molecular level, PKRA7 inhibits PK2-induced expression of certain pro-migratory chemokines and chemokine receptors in macrophages. Combining PKRA7 treatment with standard chemotherapeutic agents resulted in enhanced effects in xenograft models for both types of tumor. Taken together, our results indicate that the anti-tumor activity of PKRA7 can be mediated by two distinct mechanisms that are relevant to the pathological features of the specific type of cancer. This small molecule PK2 antagonist holds the promise to be further developed as an effective agent for combinational cancer therapy. / Dissertation