This thesis presents studies relating to the role of the gastrointestinal tract in postprandial blood pressure regulation. The areas that have been addressed include : ( i ) the methodological approaches to the evaluation of gastric emptying, blood pressure, splanchnic blood flow, intraluminal manometry and gut hormones and ( ii ) the pathophysiological mechanisms underlying postprandial hypotension, with a particular focus on ' gastric ' and ' small intestinal ' mechanisms and their potential therapeutic relevance. All of the studies have been either published or manuscripts have been prepared for publication. While scintigraphy represents the ' gold standard ' for the measurement of gastric emptying, recent studies suggest that three - dimensional ( 3D ) ultrasonography may also allow a precise measure of gastric emptying. Concurrent scintigraphic and ultrasonographic measurements of gastric emptying of liquids were performed in healthy young volunteers. There was a good correlation and agreement between scintigraphic measurements of gastric emptying and 3D ultrasonography after ingestion of both low - and high - nutrient drinks, indicating that 3D ultrasonography, provides a valid measure of gastric emptying of liquid meals in normal subjects. Postprandial hypotension, defined as a fall in systolic blood pressure of ≥ 20mmHg,occurring within two hours of a meal is now recognised as an important clinical problem, particularly in the elderly and in patients with type 2 diabetes. The mechanisms mediating postprandial hypotension are poorly understood. The effects of variations in concentration of intraduodenal glucose on the magnitude of the fall in blood pressure were evaluated in healthy elderly subjects. Blood pressure fell, and heart rate and blood glucose increased over time during infusions, however, there was no difference in blood pressure, heart rate or blood glucose concentrations between the study days. These observations suggest that glucose induced postprandial hypotension is a load rather, than concentration, dependent phenomenon. The effect of meal composition has been reported to influence the hypotensive response to a meal and information relating to the effects of triglyceride and protein on blood pressure is inconsistent. The comparative effects of isocaloric and isovolaemic intraduodenal infusions of glucose, triglyceride and protein on the magnitude of the postprandial fall in blood pressure and rise in heart rate and superior mesenteric artery blood flow were evaluated in healthy elderly subjects. There were comparable falls in systolic blood pressure and rises in heart rate, however, the maximum fall in systolic blood pressure occurred later after triglyceride and protein and the stimulation of superior mesenteric artery blood flow was less after protein. These observations suggest that the relatively slower systolic blood pressure response after triglyceride and protein may potentially reflect the time taken for digestion of triglyceride to free fatty acids and protein to amino acids. Acarbose is an antidiabetic drug that slows both gastric emptying and small intestinal glucose absorption. The effects of acarbose, on blood pressure, heart rate, gastric emptying of, and the glycaemic, insulin, glucagon - like peptide - 1 ( GLP - 1 ) and glucosedependent insulinotropic - polypeptide ( GIP ) responses to, an oral sucrose load were evaluated in healthy elderly subjects. Acarbose attenuated the fall in blood pressure and increase in heart rate induced by oral sucrose. Acarbose slowed gastric emptying and was associated with increased retention in the distal stomach. Stimulation of GLP - 1 may contribute to the slowing of gastric emptying and suppression of postprandial glycaemia by acarbose. These findings suggest that acarbose may represent a therapeutic option for the treatment of patients with postprandial hypotension. Recent studies indicate that gastric distension attenuates the postprandial fall in blood pressure. The effects of gastric distension on blood pressure and heart rate during intraduodenal infusion of glucose at a constant load and concentration were evaluated in healthy elderly subjects. Intragastric administration of water markedly attenuated the falls in systolic and diastolic blood pressure induced by intraduodenal glucose. Heart rate increased, with and without gastric distension, in response to intraduodenal glucose infusion but not after intraduodenal saline infusion. This study suggests that gastric distension may potentially be used as a simple adjunctive treatment in the management of postprandial hypotension. Studies employing nitric oxide synthase blockers have established, in animals, that nitric oxide mechanisms are important in the regulation of splanchnic blood flow and, hence, may effect postprandial blood pressure. The role of the nitric oxide synthase inhibitor, NG - nitro - L - arginine - methyl - ester ( L - NAME ), on gastric emptying, postprandial blood pressure, plasma insulin concentration and incretin hormone ( ie GIP and GLP - 1 ) release, following an oral glucose load, were evaluated in healthy elderly subjects. L - NAME attenuated the postprandial fall in blood pressure and increase in heart rate but had no effect on gastric emptying of glucose. L - NAME attenuated the glucose - induced rise in plasma insulin but had no effect on the incretin ( GIP and GLP - 1 ) hormone response to oral glucose. The study indicates that the magnitude of the fall in blood pressure and increase in heart rate and stimulation of insulin secretion induced by oral glucose in healthy elderly subjects are mediated by nitric oxide mechanisms by an effect unrelated to changes in gastric emptying, or the secretion of GIP and GLP - 1. Studies utilising 5 - hydroxytryptamine ( 5 - HT ) infusions in animals have demonstrated regional variations in intestinal blood flow suggesting a role for 5 - HT in postprandial haemodynamic responses. The effects of the 5 - hydroxytryptamine 3 ( 5 - HT3 ) antagonist, granisetron, on the blood pressure, heart rate, antropyloroduodenal motility and glycaemic responses to intraduodenal glucose infusion were assessed in healthy elderly subjects. Granisetron had no effect on blood pressure, heart rate or antral and pyloric motor responses but modulated the duodenal motor response, to intraduodenal glucose. This study indicates that while the cardiovascular response to intraduodenal glucose does not appear to be influenced by the stimulation of 5 - HT3 receptors, this receptor may be involved in the modulation of the duodenal motor activity. / Thesis (Ph.D.)--School of Medicine, 2006.

<p>The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity. </p><p>In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows:</p><p>Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pH_jm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed. </p><p>Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport. </p><p>Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pH_jm. </p><p>Removal of the loosely adherent mucus layer did not influence the maintenance of the pH_jm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pH_jm. </p><p>Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion. </p><p>Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa. </p><p>It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.</p>

The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity. In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows: Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pHjm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed. Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport. Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pHjm. Removal of the loosely adherent mucus layer did not influence the maintenance of the pHjm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pHjm. Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion. Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa. It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.

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. 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. 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. 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. 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. 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.

Binder-based assays are employed throughout the life sciences. Powerful signal amplification techniques have enabled detection of very rare molecule species diluted in simple buffers. Unspecific binding of primary binders leads to increased background in more complex samples. By requiring two recognition events, ligation-based molecular analyses provide highly specific detection of biomolecules in complex samples. We developed a highly multiplexed padlock-ligation assay targeting signature sequences in the hemagglutinin and neuraminidase genes. From a panel of 77 avian influenza isolates of all major serotypes, 97% were genotyped correctly in accordance with previous classifications by classical diagnostic methods (Paper I). Alternative splicing is an important mechanism expanding the proteome. Current analysis techniques fail to provide sequences of complete transcripts beyond the read length of sequencing instruments. We devised and implemented a strategy to compress the sequence information contained in the splicing pattern of a transcript into the presence or absence of sequence-blocks. We demonstrate that this assay yields information about the splicing patterns in thousands of transcripts from cellular cDNA (Paper II). Expression changes of mucin proteins and glycosylation structures are frequently observed from the early stages of cancer development. Expression of mucin 2 and sialyl-Tn are common features of intestinal metaplasia and gastric cancer, and are known to co-locate. Here we have developed an in situ proximity ligation assay (PLA) directed against mucin 2 and sialyl-Tn. Our study on intestinal metaplasia and gastric cancer tissue sections identified mucin 2 as a major carrier of sialyl-Tn in these conditions, and demonstrated how conveniently glycosylation of proteins can be studied by in situ PLA (Paper III). This thesis shows how the dual recognition requirement of ligation-based assays can be employed to detect target molecules with high specificity, to analyze several sequence features of nucleic acids or to study the proximity of two antigens in situ.

The current general economic and food crises have generated an unsettled future for food and feed production and prices in general. Increasing demand, prices and fluctuations in supply in world markets for fishmeal, fish oil, soybean meal, maize and wheat meal emphasize the need to reduce the dependence of the fish feed industry on these ingredients by increasing choices among a wider range of raw materials. Legume seed such as peas, chickpeas and faba beans are promising ingredients for aquafeeds due to their high protein compared to cereals but also for their energy content. The objective of the present study was to investigate the use of these legumes in both high and low inclusion level in diets for the two main species farmed in the Mediterranean countries namely, European seabass (Dicentrarchus labrax L.) and gilthead seabream (Sparus aurata L.). In Chapter 3 the effects of different processing conditions were examined on whole seed flours of tested ingredients with respect to both nutritional and antinutritional factors and physical characteristics of the experimental diet pellets including high and low levels of each legume. Extrusion of raw material resulted in a clear reduction in trypsin inhibitors (TI) with chickpeas showing a decrease of up to 90% and complete inactivation for wheat flour, while for peas and faba beans reduction was less than 50% in most cases. Extrusion processing was less effective in the reduction of phytic acid and total tannins, occasionally reaching 22% and 18% respectively. Oligosaccharides and total NSP were not drastically affected by processing, however faba bean NSP showed greater reduction. A redistribution of soluble and insoluble NSP fractions was noted for chickpea and pea flours after extrusion. Physical characteristics of the pellets were not negatively affected for any of the tested diets. In Experiment I the effects of total or partial wheat substitution by legumes were investigated on nutrient digestibility, gastrointestinal evacuation rate and serum glucose response of European seabass. Use of legumes in seabass and seabream diets resulted in an overall increase in gastrointestinal evacuation time and a delay in glucose load. Specifically, gastric evacuation time was greatly delayed when seabass was fed a diet with high levels (30%) of chickpeas, while foregut evacuation time was mostly delayed by the diet including a high level (30%) of faba beans. In addition, glucose levels in seabass serum were also affected by the type of carbohydrates ingested with wheat starch showing more rapid increase and decrease of glucose compared to fish fed pea and chickpea diets, while faba bean starch resulted in a lower glucose peak. In Experiment II growth, digestibility, hematological parameters, histological effects and fillet organoleptic characteristics and the interaction between starch inclusion level (8% and 16% or 17% and 35% of legumes respectively) and legume type were estimated when tested legumes replaced wheat in European seabass diets. Digestibility coefficients were satisfactory for all nutrients (&gt;93%) while legume diets at a low level had beneficial effects on growth parameters when compared to the control diet, with chickpeas showing a significant improvement in SGR (P&lt;0.05). High level legume diets did not result in any negative effect on growth. HSI was increased with increasing starch/legume inclusion in the feed and serum glucose also increased for fish fed high levels of faba beans and chickpeas. Carcass proximate composition was not affected by replacement of wheat in the diets, excluding the increase of fat content in fish fed chickpeas. Sensory analysis showed no differences between fish fed the control and high legume inclusion diets. Lastly in Experiment III growth, hematological parameters, histological effects and the interaction between starch inclusion level (low and high) and legume type were evaluated when tested legumes were included in gilthead seabream diets. Decreased, but not significantly so, growth was observed for all diets including legumes compared to the control. Poorer SGR were observed for pea and faba bean diets when these legumes were included at high levels. Liver glycogen increased with increasing starch level, but HSI did not differ significantly for any of the diet treatments. Histological examination of hindgut did not show pathological effects, such as enteritis, for in either species or for any of the diets. Increased absorptive vacuoles were found for control and pea diets (high level) only for seabass. The findings of this thesis showed that the two important species cultivated in Mediterranean countries responded differently to the same raw materials used at high levels in the diets. Overall legumes had a strong effect on gastrointestinal evacuation reducing the rate of feed or digesta passage. Peas, chickpeas and faba beans successfully replaced wheat in seabass diets resulting in improved growth coefficients. However, when the same legumes included in seabream diets growth performance was not improved compared to the wheat based diet.

Η παχυσαρκία και οι σχετιζόμενες με αυτήν παθολογικές καταστάσεις συνιστούν μία από τις κυριότερες αιτίες θανάτου παγκοσμίως, με τα επίπεδά της να αυξάνονται σε ανησυχητικό βαθμό. Επιδημιολογικές έρευνες σε ασθενείς με μεταβολικό σύνδρομο έδειξαν ευθεία συσχέτιση μεταξύ παχυσαρκίας και χαμηλών επιπέδων HDL χοληστερόλης πλάσματος, ενώ μελέτες σε πειραματικά μοντέλα ποντικών αποδεικνύουν πως η συσχέτιση αυτή είναι αιτιολογική. Η HDL είναι ένα μίγμα λιποπρωτεϊνικών σωματιδίων που, ανάλογα με τη σύστασή τους σε λιπίδια, μπορούν να είναι δισκοειδή ή σφαιρικά. Η σημαντικότερη αθηροπροστατευτική δράση της HDL οφείλεται στο γεγονός ότι η συγκεκριμένη λιποπρωτεΐνη συλλέγει την περίσσεια χοληστερόλης από τους περιφερικούς ιστούς και τη μεταφέρει στο ήπαρ, όπου καταβολίζεται, μια διαδικασία γνωστή και ως ανάστροφη μεταφορά χοληστερόλης. Κύρια πρωτεΐνη της HDL είναι η απολιποπρωτεΐνη Α-Ι (apoA-I), η οποία αλληλεπιδρώντας με τον μεταφορέα λιπιδίων ABCA1 προάγει την de novo σύνθεση δισκοειδών HDL σωματιδίων, τα οποία μετατρέπονται σε σφαιρικά με τη δράση του ενζύμου LCAT. Μία πρόσφατη μελέτη έδειξε ότι οι απολιποπρωτεΐνες E (apoE) και CIII (apoCIII) είναι ικανές να προάγουν την de novo βιογένεση HDL σωματιδίων ανεξάρτητα από την apoA-I. Η παρατήρηση αυτή ενίσχυσε την ιδέα ότι ο πληθυσμός της HDL είναι ένας συνδυασμός διαφορετικών σωματιδίων που έχουν διακριτή απολιποπρωτεϊνική σύνθεση. Επιπλέον, μεταβολές στις αναλογίες των απολιποπρωτεϊνών της HDL φαίνεται να καθορίζουν την κατανομή και τη λειτουργικότητα των υποπληθυσμών της. Στην παρούσα μελέτη στόχος ήταν ο δομικός και λειτουργικός χαρακτηρισμός της HDL σε ασθενείς με υπερνοσογόνο παχυσαρκία που υποβλήθηκαν σε χολοπαγκρεατική εκτροπή με γαστρική παράκαμψη κατά Roux en Y. Μελετήθηκαν 20 ασθενείς με υπερνοσογόνο παχυσαρκία, πριν και μετά την χειρουργική επέμβαση, και 7 υγιή άτομα ελέγχου. Απομονώθηκε πλάσμα από την ομάδα ελέγχου και από τους 20 ασθενείς πριν την επέμβαση καθώς και έξι μήνες μετά. Ακολούθησε κλασματοποίηση λιποπρωτεινών του πλάσματος με υπερφυγοκέντρηση σε βαθμίδωση πυκνότητας KBr και ανάλυση των κλασμάτων με Western Blot για ανίχνευση και ποσοτικοποίηση των επιπέδων των απολιποπρωτεινών apoA-I, apoE και apoCIII. Ακολούθησαν περαιτέρω βιοχημικές αναλύσεις των κλασμάτων, δομικές αναλύσεις με μη αποδιατακτική ηλεκτροφόρηση δύο διαστάσεων (2D-PAGE) και ηλεκτρονική μικροσκοπία, προκειμένου να υπάρξει μία πιο ξεκάθαρη εικόνα για τα σωματίδια που απαρτίζουν την HDL ενώ μετρήθηκε και η αντιοξειδωτική ικανότητα της HDL και στις τρεις ομάδες. Τέλος, μετρήθηκε η δραστικότητα του ενζύμου LCAT και συσχετίστηκε με την ηπατική εναπόθεση τριγλυκεριδίων των ασθενών. Η σειρά αναλύσεων των λιποπρωτεϊνικών κλασμάτων με Western Blot έδειξε ότι, έξι μήνες μετά την επέμβαση, υπάρχει μείωση των απολιποπρωτεϊνών A-I, E και CIII των ασθενών. Τα αποτελέσματα από την δισδιάστατη ηλεκτροφόρηση και την ηλεκτρονική μικροσκοπία αποδεικνύουν την ύπαρξη διαφορετικών σωματιδίων της HDL με διακριτή απολιποπρωτεϊνική σύνθεση, ενώ η μέτρηση του αντιοξειδωτικού δυναμικού της HDL φανερώνει τη ύπαρξη πιο λειτουργικής HDL μετά την επέμβαση. Η αυξημένη δραστικότητα της LCAT στους ασθενείς σε σχέση με την ομάδα ελέγχου και η μείωσή της μετά την επέμβαση υποδηλώνει ένα πιθανό αντιρροπιστικό μηχανισμό για την αναστολη της συσσώρευσης δισκοειδούς HDL. Έτσι προάγεται ο σχηματισμός περισσότερης ώριμης σφαιρικής HDL, ενώ αποτρέπεται και η εναπόθεση ηπατικών τριγλυκεριδίων που παρατηρείται στο ήπαρ των ασθενών αυτών. Η παρατήρηση ότι η δομή και η λειτουργικότητα της HDL βελτιώνονται στους ασθενείς έξι μήνες μετά την επέμβαση, οδηγεί στο συμπέρασμα ότι η χειρουργική επέμβαση στην οποία υποβάλλονται οι ασθενείς επιδρά θετικά στην ποιότητα της HDL. / Obesity and its related pathologies are one of the leading causes of death worldwide, with levels increasing to an alarming extent. Epidemiological studies in patients with metabolic syndrome showed a direct correlation between obesity and low levels plasma of HDL cholesterol and experimental studies in mice show that this correlation is causative. HDL is a mixture of lipoprotein particles, which, depending on their composition in lipids, may be discoidal or spherical. The most important atheroprotective action of HDL is due to the fact that this lipoprotein collects excess cholesterol from peripheral tissues and transports it to the liver where it is catabolized. The main protein of the HDL is apolipoprotein A-I (apoA-I), which interacts with the lipid carrier ABCA1 and promotes de novo synthesis of discoidal HDL particles, which are converted to spherical with the LCAT enzyme. A recent study showed that apolipoprotein E (apoE) and CIII (apoCIII) areable to promote de novo biogenesis of HDL particles regardless of apoA-I. This observation supported the idea that the population of HDL is a combination of different particles with distinct apolipoprotein composition. Moreover, changes in the apolipoprotein ratiosof HDL appear to determine the distribution and function of its subpopulations. Although HDL cholesterol (HDL-C) has been traditionally associated to atheroprotection, recently it became clear that HDL particle functionality is also a key in reducing cardiovascular mortality. To this date the effects of obesity on HDL structure and functionality remain unclear. In this study, the objective was the structural and functional characterization of HDL frommorbidly obese patients undergoing biliopancreatic diversion by Roux en Y before and six months after the operation, and in lean control subjects. We studied 20 morbidly obese patients before and after surgery, and 7 control healthy individuals. Plasma was isolated from the control group and 20 patients before surgery and six months. Plasma was fractionated by KBr density gradient ultracentrifugation and lipoprotein fractions were isolated and analyzed, by Western Blot, for detection and quantification of the levels of apolipoproteins apoA-I, apoE and apoCIII. Further biochemical analysis of fractions, structural analysis with non denaturing two-dimensional electrophoresis (2D-PAGE) and electron microscopy, in order to have a more clear picture of the particles that compose HDL. In order to determine whether or how the efficiency of HDL is affected by the operation, we performed an assay measuring the antioxidant capacity of HDL in all three groups. Finally, the activity of the LCAT enzyme was measured and was correlated with the triglyceride deposition observed in the liver of these patients. The sequence analyzes of lipoprotein fractions by Western Blot showed that six months after surgery, there was a decrease in the levels of apolipoproteins AI, E and CIII. The results from the two-dimensional electrophoresis and electron microscopy showed the existence of different particles with distinct HDL apolipoprotein composition while the increased antioxidant potential of HDL indicates the existence of a more functional HDL after surgery. The increased activity of LCAT in patients plasma compared with the control group and its reduction after surgery, suggests that perhaps there may be a saving grace that tries to overcome the accumulation of discoidal HDL and promotes the formation of more mature, spherical HDL, so as to prevent the triglyceride deposition observed in the liver of these patients. The observation that the structure and function of HDL improved six months after surgery, leads to the conclusion that the surgery undergone by patients has a positive effect on the quality of HDL.

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Šiuo metu Pasaulyje skrandžio apjuosimo reguliuojama juosta operacijos sudaro apie 43 % visų chirurginių operacijų, atliekamų nutukimui gydyti. Iki šiol nėra pilnai ištirta operacijoje naudojamų skrandį apjuosiančių reguliuojamų juostų konstrukcijos skirtumų įtaka gydymo rezultatams, taip pat nėra priimtų pacientų atrankos šiai operacijai kriterijų. Disertacijoje palyginome vienerių metų nutukimo chirurginio gydymo rezultatus naudojant skirtingas skrandį apjuosiančias reguliuojamas juostas – SAGB ir MiniMizer Extra. Nustatėme, kad skrandžio apjuosimo reguliuojama juosta operacija yra efektyvus ir saugus nutukimo gydymo būdas: vidutinis procentinis perteklinio kūno masės indekso sumažėjimas buvo 33,1 ± 21,9%; vertinant pagal BAROS, 34.1% pacientų pasiekė patenkinamą, 30,6% - gerą, 9,4% – labai gerą ir 2,4% – puikų gydymo rezultatą; pasitaikė 5 (4,9%) „didžiosios” komplikacijos. Esminių skirtumų tarp lygintų juostų efektyvumo ir komplikacijų skaičiaus po vienerių metų po operacijos nenustatyta: vidutinis procentinis perteklinio kūno masės indekso sumažėjimas SAGB ir MiniMizer Extra grupėse buvo atitinkamai 28,9 ± 21,3% ir 36,8 ± 22.1%, p=0.075, o „didžiųjų” komplikacijų skaičius atitinkamai 0 (0%) ir 5 (9.3%), p=0.069. 40 metų ir vyresni pacientai geresnių rezultatų pasiekė naudojant MiniMizer Extra juostą - vidutinis procentinis perteklinio kūno masės indekso sumažėjimas buvo 37,5 ± 20,8% prieš 23,6 ± 13,8 % SAGB grupėje, p=0.002. Pacientai, kurių pradinis KMI ≤ 47, geresnių... [toliau žr. visą tekstą] / It has been estimated that LAGB represents about 42% of bariatric operations performed worldwide. There are a number of different adjustable gastric bands available. Few attempts have been made to compare the influence of band design differences for efficiency and complication rate. There are no accepted criteria for choosing this particular operation. In the dissertation we compared one year results after adjustable gastric banding using different adjustable gastric bands – SAGB and MiniMizer Extra. We have determined that laparoscopic adjustable gastric banding is effective and safe bariatric procedure: the average percentage of initial excess body mass index loss was 33,1 ± 21,9%; 34.1% of patients achieved fair, 30,6% - good, 9,4% - very good and 2,4% - excellent results according to BAROS; only 5 (4,9%) major complications were diagnosed. No radical differences were stated between the efficiency and complication rate of the compared adjustable gastric bands: the average percentage of initial excess body mass index loss in SAGB and MiniMizer Extra groups was 28,9 ± 21,3% and 36,8 ± 22.1% respectively, p=0.075; major complication rate was 0 (0%) and 5 (9.3%) respectively, p=0.069. Patients at the age of 40 and older achieved better results using MiniMizer Extra band - the average percentage of initial excess body mass index loss was 37,5 ± 20,8% versus 23,6 ± 13,8% in SAGB group, p=0.002. Patients with initial BMI ≤ 47 achieved better results using MiniMizer Extra band... [to full text]

Seit 1983 ist das Konzept des Mukosa-assoziierten lymphatischen Gewebes (MALT) im Magen auf dem Boden einer chronischen Helicobacter(H.)-pylori-Infektion bekannt. Viele epidemiologische, biologische und molekulargenetische Studien haben die Rolle von H. pylori in der Lymphomgenese unterstützt. Bis heute wurden weltweit mehr als 650 Patienten mit gastralem MALT-Lymphom und H.-pylori-Infektion antibiotisch behandelt. Bei etwa 75% der Fälle kann mit Hilfe dieser Therapie eine komplette Lymphomremission induziert werden. Klinische prädiktive Faktoren helfen dabei, Patienten bezüglich ihres Risikos besser zu stratifizieren und damit die Probabilität des Ansprechens zu verbessern. Neue zytogenetische Erkenntnisse haben zudem dazu beigetragen, ein besseres Verständnis der Lymphomgenese zu erlangen. Mit der kürzlich beschrieben Translokation t(11;18) (q21;q21) könnte in Zukunft ein prädiktiver genetischer Faktor verfügbar sein. / The Role of Helicobacter pylori Infection for the Development and Treatment of Gastric MALT Lymphomas Since 1983, it is well known that mucosa-associated lymphoid tissue (MALT)-type lymphoma of the stomach is due to chronic Helicobacter pylori (H. pylori) infection. Many epidemiological, biological, and moleculargenetic studies have implicated the role of H. pylori in lymphomagenesis. Nowadays, more than 650 patients with gastric MALT lymphoma worldwide have been treated with antibiotics for H. pylori infection, achieving a complete remission in about 75% of cases. Clinical predictive factors help to stratify patients into risk groups, and help to predict the probability of lymphoma remission. New insights into cytogenetics have also contributed to the understanding of lymphomagenesis, and with the newly identified translocation t(11;18)(q21;q21) we might have also a genetic factor at hand to predict treatment response. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.