Elektromagnetiska störningar kan orsaka stora och allvarliga problem både i land och ombord på fartyg. Störningar som kommer in i kontrollerade utrymmen via kablage kan förhindras genom speciellt framtagna kabelgenomföringar. Dock gäller att dessa är installerade korrekt och syftet med detta arbete är att ta fram en principmodell för ett portabelt kontrollinstrument för kontroll av elektromagnetisk kompatibilitet (EMC).   Genom att ta delar ur flertalet internationella standarder inom EMC-området togs en principmodell för kontrollinstrumentet fram. Genom simulering kunde delar av principen fastställas och sedan utfördes praktiska prover där testuppsättningen hade sitt ursprung i en vedertagen och beprövad uppsättning.   Proverna visade på att principmodellen fungerar. Dock uppnådde inte modellens mätenhet samma mätnoggranhet som referensinstrumentet och dämpningar i de framtagna kretsarna skiljde sig från de framräknade värdena.

Content: The braiding structure of leather fibers has not been understood clearly and it is very useful and interesting to study it. Microscopic X-ray tomography (MCT) technology can produce cross-sectional images of the leather without destroying its structure. The three-dimensional structure of leather fibers can be reconstructed by using MCT slice images, so as to show the braiding structure and regularity of leather fibers. The denoising and segmentation of MCT slice images of leather fibers is the basic procedure for three-dimensional reconstruction. In order to study the braiding structure of leather fibers in the round, the image of resinembedded leather fibers MCT slices and in situ leather fibers MCT slices were analyzed and processed. It is showed that the resin-embedded leather fiber MCT slices were quite different from that of in situ leather fiber MCT slices. In-situ leather fiber MCT slice image could be denoised relatively easily. But denoising of resin-embedded leather fiber MCT slice image is a challenge because of its strong noise. In addition, some fiber bundles adhere to each other in the slice image, which are difficult to be segmented. There are many methods of image denoising and segmentation, but there is no general method to process all types of images. In this paper, a series of computer-aided denoising and segmentation algorithms are designed for in-situ MCT slice images of leather fibers and resin-embedded MCT slice images. The fiber bundles in wide field MCT images are distributed densely, adherent to each other. Many fiber bundles are separated in one image and tightly bound in another. This brings great difficulties to image segmentation. To solve this problem, the following segmentation methods are used: Grayscale-threshold segmentation method, The region-growing segmentation method, Three-dimensional image segmentation method. The denoising and segmentation algorithm proposed in this paper has remarkable effect in processing a series of original MCT slice images and resin-embedded leather fibers MCT slice images. A series of threedimensional images based on this work demonstrate the fine spatial braiding structure of leather fiber, which would help us to understand the braiding structure of leather fibers better. Take-Away: presentation ppt, Figures

Hintergrund: Bei der Herzinsuffizienz mit erhaltener Ejektionsfraktion (HFpEF) handelt es sich um ein komplexes Krankheitsbild, das mit steigenden Hospitalisierungsraten an immer zunehmender Bedeutung im Gesundheitssystem gewinnt. Trotz hoher Mortalitätsraten hat sich keine Standardtherapie etabliert und bisher existieren keine erfolgreichen Behandlungsmaßnahmen. Zudem macht die HFpEF die Hälfte aller Herzinsuffizienzfälle aus, was die Zweckmäßigkeit der Erforschung einer effektiven Therapie hervorhebt. Als ein der entscheidenden Faktoren in der Pathophysiologie der Erkrankung wird die endotheliale Störung gestellt. Mit Reduktion der NO-Bioverfügbarkeit im Endothelium führt die endotheliale Störung zur LV -Versteifung mit diastolischer Dysfunktion des Herzens. Das körperliche Training und daraus resultierende Scherkräfte im Blutgefäß triggern eine HDL-vermittelte Stickstoffmonoxid Synthese. Die vasodilatative, eNOS-steigernde Funktion des HDL kann bei Herzinsuffizienten gestört sein. Eine entsprechende Trainingsmodalität könnte sich jedoch als Endothelium-schützend zeigen. Fragestellung: Ziel dieser Dissertation ist die Erforschung, ob die HDL-Funktion von Patienten mit HFpEF durch das Hochintensive Intervalltraining (90-95 % der maximalen HF) oder Moderat-Intensives Kontinuierliches Ausdauertraining (60-70 % der maximalen HF) beeinflussbar ist. Im Fokus der Untersuchungen stehen die HDL-gesteuerte eNOS- Funktion (Funktion der endothelialen Stickstoffmonoxid-Synthase), die durch die Phosphorylierung an unterschiedlichen Aminosäureresten im Molekül ausgewertet wird, die PON-1 Aktivität (Paraoxonase-1), die für anti-oxidative Rolle des HDL spricht, sowie die Konzentrationen von TBARS (Thiobarbitursäure-reaktive Substanzen), die als Indikatoren der gesteigerten Lipidperoxidation dienen. Material und Methoden: Um die Fragen zu klären, wurden die Probanden in drei Gruppen randomisiert: 1) HIIT (Hochintensives Intervalltraining), 2) MCT (Moderat-Intensives Kontinuierliches Ausdauertraining) und 3) CG (Kontrollgruppe). Vor, während und nach den verschiedenen Trainingsinterventionen wurde das HDL durch Ultrazentrifugation aus dem Blutserum der Probanden isoliert. Im Anschluss daran erfolgte die Inkubation der gewonnenen HDL-Isolate mit humanen Aortenendothelzellen. Mittels Western Blot wurde die HDL-induzierte eNOS-Phosphorylierung an der aktivierenden Position Ser1177 (die zur Steigerung der eNOS-Aktivität führt) und an der deaktivierenden Position Thr 495 (die zur Hemmung der eNOS-Aktivität führt) ermittelt. Aktivierende Phosphorylierung der eNOS geht mit einer gesteigerten NO-Produktion einher. Zur Klärung, wie weit modifizierbar die Endothelium-schützende Rolle des HDL ist und welche Korrelationen damit einhergehen, wurde anti-oxidative Funktion des HDL gemessen. Dazu diente die Messung der Aktivität des assoziierten Enzymes - Paraoxonase-1 (PON-1), das die Lipoproteine vor oxidativer Modifikation schützt. Die protektive Eigenschaft des HDL lässt sich unter anderem durch reaktive Sauerstoffspezies modifizieren. Die reduzierte PON-1 Aktivität kann mit gesteigerter Lipidperoxidation mit daraus entstehenden Fettsäure-Radikale einhergehen. Als Indikator wurde in der vorliegenden Studie die Konzentration an Thiobarbitursäure- reaktiver Substanzen (TBARS) gemessen. Ergebnisse/ Beobachtungen: Durch das körperliche Training konnte man einen Anstieg der eNOS-Phosphorylierung an Ser1177 hervorrufen. Nach dem ersten supervidierten Teil des HIIT kam es zu einer signifikanten HDL-induzierten eNOS-Phosphorylierung an Ser 1177. Weder nach HIIT noch nach MCT konnte jedoch ein signifikanter Rückgang der eNOS Phosphorylierung an der deaktivierenden Position Thr495 festgestellt werden. Bei der Betrachtung der eNOS-Phosphorylierung in der MCT- und Kontrollgruppe fielen keine signifikanten Unterschiede auf. Bei HIIT Probanden ergaben sich signifikant erhöhte Werte von PON-1 Aktivität sowohl im Serum als auch im HDL. In MCT- und Kontrollgruppe konnten hingegen keine signifikante Steigerung der PON-1 Aktivität nachgewiesen werden. Bei der Betrachtung von erhobenen Daten dieser Arbeit fallen erhöhte Werte von TBARS- Konzentrationen bei allen Probanden auf. Es kam allerdings zu keinen signifikanten Unterschieden nach den Trainingsinterventionen. Schlussfolgerungen: Die vorliegende Studie liefert die Erkenntnisse, dass das Hochintensive Intervalltraining eine signifikant gesteigerte HDL-vermittelte eNOS Phosphorylierung, die ebenfalls mit signifikant erhöhter PON-1 Aktivität einhergeht, bei HFpEF-Erkrankten induziert. Ferner aus den erhobenen Daten lässt sich ableiten, dass die Compliance bei allen Probandengruppe jeweils höher während eines überwachten Trainings als während einer home-basierten Intervention war. Insgesamt kann man daraus spekulieren, dass HIIT eine verbesserte endotheliale Funktion des HDL hervorrufen könnte und eine mögliche effektive Therapiemethode der HFpEF in Zukunft darstellen würde. Eine Nutzung dieser Methode bleibt offen und bedarf weiterer Forschungen.:Inhaltsverzeichnis I Tabellenverzeichnis IV Abbildungsverzeichnis V Abkürzungsverzeichnis VI 1 Einleitung 3 1.1 Die Herzinsuffizienz mit erhaltener Ejektionsfraktion 3 1.1.1 Definition der Herzinsuffizienz, Klinisches Bild, Einteilung nach der Pathophysiologie 3 1.1.2 Epidemiologie der HFpEF 3 1.1.3 Pathomechanismus der HFpEF 4 1.1.4 HFpEF vs. HFrEF 11 1.1.5 Diagnose der HFpEF 12 1.1.6 Behandlungsmöglichkeiten 12 1.2 Körperliches Training 14 1.2.1 Belastungsintoleranz bei HFpEF 14 1.2.2 Hochintensives Intervalltraining (HIIT) und Moderat-Intensives Kontinuierliches Ausdauertraining (MCT) 15 1.3 High density lipoproteins 16 1.3.1 HDL bei Herzinsuffizienz 16 1.3.2 Funktionen und Bedeutung von HDL-Partikeln 17 1.4 Zielsetzung und Fragestellung 19 2 Material 20 2.1 Serum 20 2.2 Zellkulturmaterial 20 2.3 Kulturmedium 20 2.4 Chemikalien und Lösungen 20 2.5 Färbelösungen 20 2.6 Antikörper 20 2.7 Chemilumineszenz 20 2.8 Sonstige Materialien 21 2.9 Geräte 21 2.10 Software 21 3 Methoden 22 3.1 Studiendesign 22 3.2 Trainingsintervention 23 3.3 Isolation des HDL 24 3.3.1 Vorarbeiten 24 3.3.2 HDL Isolation 24 3.3.3 HDL Aufreinigung 25 3.4 Bestimmung der Proteinkonzentration nach der BCA-Methode 25 3.5 Stimulation der Zellen 26 3.6 Western Blot 26 3.7 Gelelektrophorese 27 3.8 Proteintransfer 28 3.9 Immundetektion 29 3.10 Chemilumineszenz 29 3.11 PON-1 Aktivität 30 3.12 TBARS 30 3.13 Statistische Analyse 30 4 Ergebnisse 31 4.1 Charakterisierung der Patienten 31 4.2 Patientendaten 32 4.3 Qualität des isolierten HDL 38 4.4 Die HDL-induzierte eNOS-Phosphorylierung 40 4.5 Aktivität der Paraoxonase 1 (PON-1) 44 4.6 TBARS-Konzentration im Serum 47 5 Diskussion 49 5.1 Hauptaussagen 49 5.1.1 Endotheliale Effekte des Trainings via HDL 50 5.1.2 Trainingsmodalitäten als potentielle Therapie 52 5.1.3 Denkbarer molekularer Mechanismus für die Regulation von endothelialen Funktionen des HDL 55 5.1.4 Quantitative vs. qualitative Auswertung der HDL Funktion 57 5.1.5 Unterschiede bei der Einhaltung der verschiedenen Trainingsprotokollen 59 5.1.6 Ausblick für zukünftige Forschungsarbeiten 61 5.1.7 Studienlimitationen 63 6 Zusammenfassung 65 7 Summary 67 8 Literaturverzeichnis 69 9 Anlage 1 88 10 Anlage 2 89 11 Curriculum vitae 90 12 Danksagung 91 Tabellenverzeichnis Tabelle 1: Reagenzien zur Vorbereitung eines 8 % und 12 % SDS-Polyacrylamidgels 27 Tabelle 2: Die verwendeten Antikörper zur Detektion der Proteine 29 Tabelle 3: Patientendaten zu Beginn der Studie -V1 32 Tabelle 4: Patientendaten zu den Zeitpunkten V1, V2, V3 33 Tabelle 5: Medikation 34 Tabelle 6: Lipidprofil 36 Tabelle 7: Ergospirometrie 37 Abbildungsverzeichnis Abbildung 1: Pathomechanismus der myokardialen Dysfunktion (übernommen aus Paulus & Tschöpe, 2013) 6 Abbildung 2: Entstehung der myokardialen Dysfunktion durch Veränderungen innerhalb extrazellulärer Matrix und Kardiomyozyten bei Übergewicht und Diabetes mellitus (DM) 7 Abbildung 3: Komorbiditäten bei HFpEF als Trigger für diastolische Dysfunktion 9 Abbildung 4: NO Synthese als Antwort auf Shear Stress 10 Abbildung 5: Schematische Darstellung, wie ein körperliches Training das Krankheitsfortschreiten sowie HDL-induzierte NO-Produktion beeinflusst (übernommen aus Adams et al., 2013) 18 Abbildung 6: Studiendesign 22 Abbildung 7: Trainingsprotokoll, MCT-Moderat-Intensives Kontinuierliches Ausdauertraining, HIIT- Hochintensives Intervalltraining, HRpeak- maximale Herzfrequenz (übernommen aus Suchy et al., 2014) 23 Abbildung 8: Positionieren der Kanülenspitze und Entnahme des HDL 25 Abbildung 9: SDS-Page nach Färbung mit Coomassie-Blau zum Nachweis von HDL mit Größenmarker, BSA-Standard und den HDL-Proben (10 μg, 20 μg und 30 μg des Proteins) 38 Abbildung 10: Die Immundetektion der gebundenen Antikörper Apo-Protein A 1 durch eine Chemilumineszenz-Reaktion mit Größenmarker (M) zum Nachweis von HDL. Apo-AI, das Hauptprotein des HDL, mit einer Molekülgröße von 28 kDa wurde in 1,95 μg, 0,99 μg, 0,5 μg und 0,099 μg des HDL-Isolates identifiziert 39 Abbildung 11: Die eNOS-Phosphorylierung an Ser1177 zu den Zeitpunkten V1, V2, V3 bei der HIIT-(C), MCT-(B) und CG-Gruppe-(A) 40 Abbildung 12: Die eNOS-Phosphorylierung an Thr495 zu den Zeitpunkten V1, V2, V3 bei der HIIT-(F), MCT-(E) und CG-Gruppe(D) 42 Abbildung 13: Aktivität der Paraoxonase-1 im HDL 45 Abbildung 14: Aktivität der Paraoxonase-1 im Serum 46 Abbildung 15: TBARS-Konzentration im Serum [μmol/l] 48 / Background: Heart failure with preserved ejection fraction (HFpEF) is a complex disease. Due to its increasing hospitalization rates, HFpEF is gaining importance in the healthcare system. Despite the high mortality rate, there is no successful treatment procedure and no standard therapy has been established. Moreover, HFpEF makes up half of all heart failure cases, which underlines the usefulness of finding the effective therapy. One of the determining factors of HFpEF pathophysiology is endothelial dysfunction. The reduction of NO-bioavailability in endothelium and consequently endothelial dysfunction provides to LV stiffness and diastolic dysfunction of the heart. The exercise training triggers shear stress inside the blood vessels and results in HDL-mediated nitric oxide synthesis. In heart failure patients, the eNOS-increasing and vasodilative function of HDL can be impaired. However, a suitable training modality could work as endothelium-protective. Aims: The present doctoral thesis aims to investigate the influence of high-intensity interval training (peak HR 90-95%) and moderate-intensity continuous training (peak HR 60-70%) on the function of HDL by HFpEF patients. This study focuses on HDL-regulated eNOS function (function of endothelial nitric oxide synthesis), which is evaluated by phosphorylation of different aminoacids residues in the molecule. Furthermore, we determined the activity of PON-1 (paraoxonase-1), which speaks of the antioxidative role of HDL, as well the concentration of TBARS (thiobarbituric acid reactive substances), which indicate increased lipid peroxidation. Material and methods: To clarify the questions, the probands were randomized to three groups: 1) HIIT (high-intensity interval training, 2) MCT (moderate-intensity continuous training) and 3) CG (control group). Before, during, and after different training interventions the HDL was isolated from the blood serum of probands by ultracentrifugation. Further, the HDL isolates were incubated with human aortic endothelial cells. The HDL-induced eNOS phosphorylation at the activating position Ser1177 (which results in increased activity of eNOS) and deactivating Thr495 (which results in inhibition of eNOS activity) were assessed by western blotting. The activated phosphorylation of eNOS leads to increased NO production. Subsequently, to investigate how modifiable the endothelial-protective role of HDL is and to find the possible correlation, the antioxidative function of HDL was evaluated. The latter was assessed by measuring the activity of the associated enzyme PON-1 (paraoxonase-1), which protects the lipoproteins against oxidative modifications. The protective property of HDL might be among others modified by reactive oxygen species. The reduced activity of PON-1 can be associated with increased lipid peroxidation and therefrom resulting fatty acids radicals. In this study, the amount of fatty acids radicals was indicated by the concentration of TBARS (thiobarbituric acid-reactive substances). Results and observations: Exercise training can increase phosphorylation at Ser1177. Indeed, the first supervised part of HIIT resulted in a significant increase of HDL-induced eNOS-Phosphorylation at Ser1177. However, neither after HIIT nor after MCT any significant decline of eNOS phosphorylation at deactivated position Thr495 could be demonstrated. Regarding the eNOS phosphorylation after MCT and in CG, no significant changes were observed. Furthermore, significantly increased activity of PON-1 in serum as well as in HDL was observed after HIIT. But, neither in MCT nor in the control group any significant increase in PON-1 activity was observed. The increased concentration of TBARS was detected in all groups. After the interventions, no significant differences concerning the concentration of TBARS were demonstrated in any group. Conclusions: High-intensity interval training by HFpEF patients results in increased HDL- induced eNOS phosphorylation, which is accompanied by significantly increased activity of PON-1. Therefore, we can speculate that HIIT could enhance the endothelial function of HDL and would be in the future one of the possible effective treatment methods for HFpEF. Furthermore, this study derives that compliance in all groups was higher during the supervised training than during home-based intervention. Eventually, the usefulness of HIIT in clinical settings requires further investigation.:Inhaltsverzeichnis I Tabellenverzeichnis IV Abbildungsverzeichnis V Abkürzungsverzeichnis VI 1 Einleitung 3 1.1 Die Herzinsuffizienz mit erhaltener Ejektionsfraktion 3 1.1.1 Definition der Herzinsuffizienz, Klinisches Bild, Einteilung nach der Pathophysiologie 3 1.1.2 Epidemiologie der HFpEF 3 1.1.3 Pathomechanismus der HFpEF 4 1.1.4 HFpEF vs. HFrEF 11 1.1.5 Diagnose der HFpEF 12 1.1.6 Behandlungsmöglichkeiten 12 1.2 Körperliches Training 14 1.2.1 Belastungsintoleranz bei HFpEF 14 1.2.2 Hochintensives Intervalltraining (HIIT) und Moderat-Intensives Kontinuierliches Ausdauertraining (MCT) 15 1.3 High density lipoproteins 16 1.3.1 HDL bei Herzinsuffizienz 16 1.3.2 Funktionen und Bedeutung von HDL-Partikeln 17 1.4 Zielsetzung und Fragestellung 19 2 Material 20 2.1 Serum 20 2.2 Zellkulturmaterial 20 2.3 Kulturmedium 20 2.4 Chemikalien und Lösungen 20 2.5 Färbelösungen 20 2.6 Antikörper 20 2.7 Chemilumineszenz 20 2.8 Sonstige Materialien 21 2.9 Geräte 21 2.10 Software 21 3 Methoden 22 3.1 Studiendesign 22 3.2 Trainingsintervention 23 3.3 Isolation des HDL 24 3.3.1 Vorarbeiten 24 3.3.2 HDL Isolation 24 3.3.3 HDL Aufreinigung 25 3.4 Bestimmung der Proteinkonzentration nach der BCA-Methode 25 3.5 Stimulation der Zellen 26 3.6 Western Blot 26 3.7 Gelelektrophorese 27 3.8 Proteintransfer 28 3.9 Immundetektion 29 3.10 Chemilumineszenz 29 3.11 PON-1 Aktivität 30 3.12 TBARS 30 3.13 Statistische Analyse 30 4 Ergebnisse 31 4.1 Charakterisierung der Patienten 31 4.2 Patientendaten 32 4.3 Qualität des isolierten HDL 38 4.4 Die HDL-induzierte eNOS-Phosphorylierung 40 4.5 Aktivität der Paraoxonase 1 (PON-1) 44 4.6 TBARS-Konzentration im Serum 47 5 Diskussion 49 5.1 Hauptaussagen 49 5.1.1 Endotheliale Effekte des Trainings via HDL 50 5.1.2 Trainingsmodalitäten als potentielle Therapie 52 5.1.3 Denkbarer molekularer Mechanismus für die Regulation von endothelialen Funktionen des HDL 55 5.1.4 Quantitative vs. qualitative Auswertung der HDL Funktion 57 5.1.5 Unterschiede bei der Einhaltung der verschiedenen Trainingsprotokollen 59 5.1.6 Ausblick für zukünftige Forschungsarbeiten 61 5.1.7 Studienlimitationen 63 6 Zusammenfassung 65 7 Summary 67 8 Literaturverzeichnis 69 9 Anlage 1 88 10 Anlage 2 89 11 Curriculum vitae 90 12 Danksagung 91 Tabellenverzeichnis Tabelle 1: Reagenzien zur Vorbereitung eines 8 % und 12 % SDS-Polyacrylamidgels 27 Tabelle 2: Die verwendeten Antikörper zur Detektion der Proteine 29 Tabelle 3: Patientendaten zu Beginn der Studie -V1 32 Tabelle 4: Patientendaten zu den Zeitpunkten V1, V2, V3 33 Tabelle 5: Medikation 34 Tabelle 6: Lipidprofil 36 Tabelle 7: Ergospirometrie 37 Abbildungsverzeichnis Abbildung 1: Pathomechanismus der myokardialen Dysfunktion (übernommen aus Paulus & Tschöpe, 2013) 6 Abbildung 2: Entstehung der myokardialen Dysfunktion durch Veränderungen innerhalb extrazellulärer Matrix und Kardiomyozyten bei Übergewicht und Diabetes mellitus (DM) 7 Abbildung 3: Komorbiditäten bei HFpEF als Trigger für diastolische Dysfunktion 9 Abbildung 4: NO Synthese als Antwort auf Shear Stress 10 Abbildung 5: Schematische Darstellung, wie ein körperliches Training das Krankheitsfortschreiten sowie HDL-induzierte NO-Produktion beeinflusst (übernommen aus Adams et al., 2013) 18 Abbildung 6: Studiendesign 22 Abbildung 7: Trainingsprotokoll, MCT-Moderat-Intensives Kontinuierliches Ausdauertraining, HIIT- Hochintensives Intervalltraining, HRpeak- maximale Herzfrequenz (übernommen aus Suchy et al., 2014) 23 Abbildung 8: Positionieren der Kanülenspitze und Entnahme des HDL 25 Abbildung 9: SDS-Page nach Färbung mit Coomassie-Blau zum Nachweis von HDL mit Größenmarker, BSA-Standard und den HDL-Proben (10 μg, 20 μg und 30 μg des Proteins) 38 Abbildung 10: Die Immundetektion der gebundenen Antikörper Apo-Protein A 1 durch eine Chemilumineszenz-Reaktion mit Größenmarker (M) zum Nachweis von HDL. Apo-AI, das Hauptprotein des HDL, mit einer Molekülgröße von 28 kDa wurde in 1,95 μg, 0,99 μg, 0,5 μg und 0,099 μg des HDL-Isolates identifiziert 39 Abbildung 11: Die eNOS-Phosphorylierung an Ser1177 zu den Zeitpunkten V1, V2, V3 bei der HIIT-(C), MCT-(B) und CG-Gruppe-(A) 40 Abbildung 12: Die eNOS-Phosphorylierung an Thr495 zu den Zeitpunkten V1, V2, V3 bei der HIIT-(F), MCT-(E) und CG-Gruppe(D) 42 Abbildung 13: Aktivität der Paraoxonase-1 im HDL 45 Abbildung 14: Aktivität der Paraoxonase-1 im Serum 46 Abbildung 15: TBARS-Konzentration im Serum [μmol/l] 48

No description available.

Le catabolisme exacerbé du glucose et de la glutamine est actuellement reconnu comme une caractéristique des cellules cancéreuses, qui leur procure un avantage prolifératif via la production et l’accumulation de plusieurs métabolites au niveau du microenvironnement. Parmi ces métabolites, l’acide lactique représente une molécule de signalisation clé, favorisant la migration et les métastases. Mon projet de thèse s’inscrit dans le contexte d’une étude du métabolisme glycolytique associé aux cellules tumorales à division rapide. Durant ce projet, nous nous sommes intéressés à la caractérisation génétique et fonctionnelle des transporteurs MCT (MonoCarboxylate Transporters) 1 et 4, qui sont des symporteurs H+/lactate dont l’expression membranaire et la fonctionnalité requièrent la liaison avec une protéine chaperonne : CD147/BASIGINE (BSG). Afin de mieux explorer la physiologie des complexes MCT/BSG, et valider le ciblage de l’export d’acide lactique comme une nouvelle approche anti-cancer, nous avons développé une stratégie visant à invalider le gène BSG et/ou MCT4, en utilisant la technologie des Zinc Finger Nucleases (ZFN), dans des lignées cellulaires cancéreuses humaines de côlon, poumon et glioblastome. D’abord, nous avons démontré, que l’effet pro-tumoral majeur de BSG est lié à son action directe sur la stabilisation des MCTs au niveau des tumeurs glycolytiques et non pas à la production des metalloprotéases. Ensuite, nous avons démontré pour la première fois que l’inhibition concomitante de MCT1 et MCT4 est nécessaire pour induire une baisse significative de la tumorigénécité in vivo. / Enhanced glucose and glutamine catabolism has become a recognized feature of cancer cells, leading to accumulation of metabolites in the tumour microenvironment, which offers growth advantages to tumours. Among these metabolites is emerging as a key signalling molecule that plays a pivotal role in cancer cell migration and metastasis. In this thesis, we focused on the genetic and functional characterization of monocarboxylate transporters (MCT) 1 and 4, which are H+/lactate symporters that require an interaction with an ancillary protein, CD147/BASIGIN (BSG), for their plasma membrane expression and function. To further explore the physiology of MCT/BSG complexes and validate the blockade of lactic acid export as an anti-cancer strategy, we designed experiments using Zinc Finger Nuclease mediated BSG and/or MCT4 gene knockouts in human colon adenocarcinoma, lung carcinoma and glioblastoma cell lines. First of all, we demonstrated that the major protumoural action of BSG is to control the energetics of glycolytic tumours via MCT1/4 activity and not to produce matrix metalloproteases. Second, we showed for the first time that combined inhibition of both MCT1 and MCT4 transporters is required to achieve a significant reduction in the tumour growth in vivo. Moreover, our findings reported that disruption of the BSG gene dramatically reduced the plasma membrane expression and lactate transport activity of both MCT1 and MCT4, leading to increased accumulation of intracellular pools of lactic and pyruvic acids, decreased intracellular pH and reduced rate of glycolysis.

Hepatic steatosis is characterised by accumulation of triacylglycerols in the cytoplasm of hepatocytes at a level that reaches 5 to 40% of the weight of the liver. Its prevalence has increased worldwide, having a strong relationship with diabetes mellitus type 2 and obesity, diseases that constitute a global epidemic. Despite having been considered for a considerable time as a benign entity, it is known that a synergic combination with other factors, such as oxidative stress, can trigger a cascade of inflammatory reactions, leading to fibrogenesis, cirrhosis and hepatocellular carcinoma. Its etiology, despite not being totally elucidated, shows a strong correlation with insulin resistence, and is actually considered a hepatic manifestation of metabolic syndrome. However, it can be triggered by other factors; such as prolonged total parenteral nutrition, bariatric surgery, proteincalory malnutrition and the use of drugs. The actual prevalence is unknown but it affects adults and children, and is emerging as the most common chronic condition of the liver in the western world. Though an effective pharmacological treatment does not exist, all patients are encouraged to reduce their ingestion of fat and to practise regular physical exercise, with the objective of increasing their daily energy expenditure. Strategies of nutritional intervention and control of associated metabolic risk factors need to be evaluated. Aiming at contributing to the discussion of the problem, this dissertation presents two articles: a literature review of the main strategies of dietetic therapy in the treatment of steatosis, dealing with energy intake and the intake of macro- and micronutrients that exert effects on the prevention, treatment and/or retard the progression of the disease; the second article refers to an experimental study of weaned Wistar rats that received a diet with substitution of soy oil with an experimental oil rich in 9 triheptanoin, a triacylglycerol of heptanoic acid (7:0), that was being used in disorders of mitochondrial oxidative metabolism. The animals that received AIN-93 diets with 0, 30 and 50% of substitution of soy oil with experimental oil developed hepatic steatosis. The histological analysis revealed half the number of severe cases of hepatic steatosis in the animals with 50% substitution in relation to those with 0% substitution. Other variables demonstrated a potential protector effect of the experimental oil against hepatic steatosis as absolute and relative liver weight. Such an effect, associated with the clinical evidence of the success of triheptanoin with several mitochondrial disorders, awakes interest in the future of its application for other disorders. / Fundação de Amparo a Pesquisa do Estado de Alagoas / A esteatose hepática é caracterizada pelo acúmulo de triacilgliceróis no citoplasma dos hepatócitos a um nível que atinge 5 a 40% do peso do fígado. Sua prevalência tem aumentado em todo o mundo devido a forte relação com o diabetes mellitus tipo 2 e a obesidade, doenças que se constituem epidemias globais. Apesar de ter sido considerada por muito tempo como uma entidade benigna, sabe-se que a combinação sinérgica com outros fatores, como o estresse oxidativo, pode desencadear reações inflamatórias em cascata, levando à fibrogênese, cirrose e ao carcinoma hepatocelular. Sua etiologia, apesar de não estar totalmente elucidada, mostra forte correlação com a resistência à insulina, sendo, atualmente, considerada a manifestação hepática da síndrome metabólica. Entretanto, pode ser desencadeada por outros fatores, como nutrição parenteral total prolongada, cirurgia bariátrica, desnutrição calórico-protéica e o uso de drogas. Embora a prevalência verdadeira seja desconhecida, atinge adultos e crianças e está emergindo como a condição crônica do fígado mais comum no mundo ocidental. Apesar de ainda não existir tratamento farmacológico eficaz, todos os pacientes são encorajados a reduzir a ingestão de gorduras e praticar exercícios físicos regulares, com o objetivo de aumentar o gasto energético diário. Estratégias de intervenção nutricional e controle dos fatores de risco metabólico associados devem ser avaliadas. Visando contribuir com a discussão do problema, esta dissertação apresenta dois artigos: uma revisão da literatura com as principais estratégias da terapêutica dietética no tratamento da esteatose, tratando de oferta energética e aporte de macro e micronutrientes que exercem efeitos na prevenção, tratamento e/ou retardo da progressão da doença; o 7 segundo artigo refere-se a um estudo experimental com ratos Wistar recém desmamados, que receberam dieta com substituição do óleo de soja por um óleo experimental rico em trieptanoína, um triacilglicerol do ácido heptanóico (7:0), que vem sendo utilizado em desordens do metabolismo oxidativo mitocondrial. Os animais que receberam dietas AIN-93 com 0, 30 e 50% de substituição do óleo de soja pelo óleo experimental desenvolveram esteatose hepática. A análise histológica revelou metade do número de casos graves de esteatose hepática nos animais com 50% de substituição em relação àqueles submetidos a 0% de substituição. Outras variáveis evidenciaram potencial efeito protetor do óleo experimental contra a esteatose, como peso absoluto e relativo do fígado. Tal efeito, associado às evidências clínicas de sucesso do uso da trieptanoína em algumas desordens mitocondriais, desperta o interesse em investigações futuras de sua aplicação terapêutica em outras desordens.

Ce travail avait pour objectif i) d’analyser les caractéristiques physiologiques et musculaires(déterminées d’après des biopsies) de rameurs poids légers entraînés, ii) de proposer une méthode de153calcul pour estimer de façon non-invasive la quantité de lactate accumulé dans l’organisme (QTLS) au cours d’un exercice épuisant sur ergomètre aviron d’après la modélisation de la cinétique lactique pendant la récupération et iii) d’explorer l’influence des caractéristiques musculaires, et de l’aptitude à échanger et à éliminer le lactate sur la capacité anaérobie des rameurs appréciée par la mesure du déficit maximal d’O2 cumulé (DMOC).Premièrement, les rameurs étudiés possédaient un rapport masse musculaire - masse corporelle élevé et leurs paramètres physiologiques et musculaires étaient caractéristiques des athlètes spécialisées en endurance.Dans un deuxième temps, nous avons démontré que QTLS était corrélé positivement à DMOC.Cette relation supporte notre hypothèse et confirme la cohérence de la méthode proposée pour calculer QTLS.Dans une dernière étude, les résultats ont démontré que DMOC était corrélée positivement à l’aptitude à éliminer le lactate. Cette dernière était également significativement corrélée à la densité capillaire et au contenu musculaire en MCT4, une protéine impliquée dans le cotransport lactate-proton à travers le sarcolemme. / The aim of this work was i) to analyse physiological and muscle characteristics (determinedfrom muscle biopsies) in trained lightweight oarsmen, ii) to propose a non-invasive method to estimatelactate accumulation in the organism (QTLS) using the blood lactate recovery kinetics in response to anall-out exercise on rowing ergometer and iii) to explore the influence of muscle characteristics andlactate exchange and removal abilities on the anaerobic capacity of our subjects determined from themeasurement of the maximal accumulated oxygen deficit (MAOD).Firstly, the studied oarsmen displayed an elevated muscle - body mass ratio and their muscleand physiological characteristics were typical of those of elite endurance athletes.Secondly, we showed that QTLS was positively correlated with MAOD. This relationshipsupports our hypothesis and reinforces the interest of our method to estimate QTLS.Finally, the results demonstrated that MAOD was positively correlated with the lactate removalability. This latter was also positively correlated with the capillary density and the muscle content ofMCT4, a protein involved in the cotransport of lactate and proton across the sarcolemma

Made available in DSpace on 2014-07-29T15:18:22Z (GMT). No. of bitstreams: 1 Rita_Cassia_Silva.pdf: 4395629 bytes, checksum: 0c215c46e6dd82bf63ddafc66ab1035c (MD5) Previous issue date: 2010-08-30 / Paving is part of infrastructure investment to maintain and enhance economic growth and conditions for improving life quality. It is an activity that depends on selection and extraction of materials and requires high investments, whose availability is often limited and requires minimization of costs at all stages. Therefore, as it promotes a great economy mainly in transport, the use of appropriate materials extracted closest to the area to be paved should be taken into account in selection stage. Besides, conventional materials suitable for use in the pavement structure, such as granular materials, are scarce. Therefore, knowledge of regional materials with appropriate characteristics to the pavement is even more important. The Brazilian experience in using tropical lateritic soils in highways has been highly promising, contradicting the conventional use of the specifications adopted in the temperate regions. This experience has brought the implementation of lateritic soils and structured for this purpose the MCT (Miniature, Compressed, Tropical) methodology. From this context, the main objective of this work is to investigate soils that have suitable properties for use in paving and potential mineral deposits. The research was then conducted in two stages. The first one came from an environmental characterization, based mainly on maps, which allowed the identification of seven points for preliminary assessment of the indicated areas. The samples collected near to the surface were tested by X-ray diffraction, expeditious disk method and chemical analysis. By analyzing these points, two were chosen, where wells were dug for the analysis of soil profile. During this second phase, soil samples collected from these wells were tested for conventional characterization and support capacity by traditional method and by the MCT in order to evaluate these soils with respect to their support capacity to application to pavements. This investigation concluded that the soil properties of the two wells were favorable for the intended use. It is noteworthy, however, that although both belong to the group of Latossolos, they showed signs of being at different stages of weathering. According to the foregoing, it is believed that this research can contribute to the investigation of lateritic clay soils for use in paving as well as to enhance the city's geotechnical information, in the case Goiania, and thereby contribute to the integrated planning of future areas to be paved. / A pavimentação é uma atividade que deve ser considerada no investimento de infra-estrutura para manter ou ampliar o crescimento econômico e as condições de melhoria da qualidade de vida da população. É uma atividade que depende da seleção e da extração de materiais adequados e exige investimentos altos, cuja disponibilidade é geralmente limitada exigindo a minimização de custos em todas as etapas. Portanto, a utilização de materiais adequados mais próximos da área a ser pavimentada é um fator que deve ser levado em conta, pois promove uma grande economia, principalmente em transporte de material. Somado a isso, tem-se que os materiais convencionais adequados, no caso os granulares, para o uso na estrutura do pavimento estão escassos. Portanto, o conhecimento dos materiais regionais com características apropriadas à pavimentação é ainda mais premente. A experiência brasileira com a utilização de solos tropicais lateríticos em pavimentação tem-se mostrado bastante promissora, contradizendo o uso das especificações convencionais adotadas nas regiões de clima temperado. Esta experiência trouxe a aplicação de solos lateríticos e a estruturação da metodologia MCT (Miniatura, Compactada, Tropical) para este fim. A partir deste contexto, este trabalho tem como principal objetivo investigar solos que apresentem propriedades adequadas ao uso em pavimentação, como possíveis jazidas minerais. Para isso, esta pesquisa foi realizada em duas etapas. A primeira delas partiu de uma caracterização ambiental, embasada principalmente nos diversos mapeamentos, o que permitiu a identificação de sete pontos para avaliação preliminar das áreas mais indicadas. As amostras, coletadas próximas da superfície, foram ensaiadas por difratometria de Raios-X, método expedito da pastilha e análise química. Com a análise destes pontos, foram escolhidas dois, onde foram escavados poços para a análise do solo em perfil. Nesta segunda etapa, as amostras de solo recolhidas desses poços foram testadas em ensaios de caracterização convencional e de capacidade suporte pelo método tradicional e pela metodologia MCT, com vista à avaliação destes solos quanto à capacidade de suporte para aplicação em pavimentos. Esta investigação possibilitou, dentre outras conclusões, a verificação de que os solos dos dois poços apresentaram propriedades consideradas favoráveis para o uso pretendido. Destaca-se, entretanto, que apesar de ambos pertencerem ao grupo dos Latossolos, eles apresentaram indícios de estarem em estágios diferentes de intemperismo. De acordo com as considerações expostas, acreditase que esta pesquisa possa contribuir com a investigação dos solos argilosos lateríticos para uso em pavimentação como também para aprimorar as informações geotécnicas da cidade, no caso Goiânia, e com isso contribuir para o planejamento integrado das futuras áreas a serem pavimentadas.

Thesis (MScAgric)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: Different substances were evaluated and compared to an antibiotic, in terms of their effect on nitrogen - and amino acid digestibilities. Two digestibility trials and one performance trial were conducted. Trials one and two apparent nitrogen (AND)- and amino acid (AAD) digestibilities were determined from digesta collected at the terminal ileum (ileal digestibility method). In Trial 3 the substances were evaluated in terms of their potential to improve production performance. Broilers were fed a maizesoya based diet throughout the three trails. In the first trial, garlic and a commercial prebiotic (Bio-Mos®), were tested and compared in terms of AND and AAD, to an antibiotic (doxycyclin, Doxyvete-SOS). A starter and finisher diet were fed as either mash or pellets. The garlic was included at 8g/kg, 13g/kg and 18g/kg to the starter and finisher diets. Bio-Mos® was added at 1g/kg, 2g/kg and 3g/kg to the starter diet, and 0.5g/kg, 1g/kg and 1.5g/kg to the finisher diet. The doxycyclin was added at 0.3 g/kg. None of the treatments had any beneficial effects in terms of AND. Feeding a pellet seem to have some negative effects in terms of AND. In general most of the treatments did not show any improvement in AAD at any determination period (day 21, 28 or 35). At day 21 and day 35, the mash diet supplemented with 18g/kg garlic had a negative effect on AAD, when compared to the negative and positive control. It doesn’t seem that feeding either a mash or a pellet had an influence on the effects exerted by the different treatments. In the second trial the influence of Bio-Mos®, a blend of organic acids, probiotics and electrolytes (Acid-Pak 4-way®) and a medium-chain triglyceride (MCT) were evaluated and compared in terms of AAD and AND, to the effect of an antibiotic, doxycyclin. The starter and finisher diets were fed as a mash. Bio-Mos® was included at 1g/kg, 2g/kg, and 3g/kg in the starter diet, and at 0.5g/kg, 1g/kg, 1.5g/kg in the finisher diet, respectively. Acid-Pak 4-way® was included at 0.4g/kg, 1g/kg and 1.6g/kg for both the starter and finisher diets. Medium-chain triglycerides (MCT) were allocated at 3g/kg, 3.6g/kg, 4.2g/kg for the starter diet, and 2.1g/kg, 2.7g/kg and 3.4g/kg for the finisher diet. An antibiotic, doxycyclin, was included at 0.3 g/kg. With AND, no treatment had any significant effect for the entire experimental period. At day 21, the treatment supplemented with MCT (3.4g/kg) had the most significant beneficial effect on AAD, when compared to the negative- and positive controls, as it increased AAD for the majority of the amino acids. The treatment with Acid-Pak 4-way® (1g/kg) had the most significant negative effect on AAD when compared to the positive control. At day 28, the treatments with Bio-Mos® (0.5g/kg and 1.5g/kg) and Acid-Pak 4-way® (0.4g/kg) had the most significant beneficial effect on AAD when compared to the positive control. It increased AAD for more than half of the 17 amino acids evaluated. The treatment supplemented with MCT (2.7g/kg) has shown the most significant negative effect on AAD, when compared to the positive control. In the third trial the effect of Bio-Mos®, Acid-Pak 4-way® and MCT on production performance was evaluated, and compared to the effects of the presence or absence of doxycyclin. Body weight (BW), body weight gain (BWG), feed intake (FI) and feed conversion ratio (FCR) were measured. The starter and finisher diets were fed as a mash. Bio-Mos®, MCT and Acid-Pak 4-way® were included at 3.0g/kg, 4.2g/kg and 1.6g/kg, respectively in the starter and finisher diets. Birds were weighed (per pen) on arrival and on days 7, 14, 21, 28, 35. Feed intake (FI) per pen was measured at days 7, 14, 21, 28 and 35, and mortality was recorded daily. In terms of BWG, Acid-Pak 4-way® had a higher BWG, when compared to the negative control, Bio-Mos® and MCT. It can be concluded that Bio-Mos®, Acid-Pak 4-way®, as well as MCT can be a possible alternatives to antibiotic supplementation. These three treatments did not necessary prove to be more effective than antibiotics, but are definitely competitive alternatives. / AFRIKAANSE OPSOMMING: Verskillende behandelings is geëvalueer en vergelyk met ‘n antimikrobiese produk, in terme van hul uitwerking op stikstof - en aminosuur verteerbaarhede. Twee verteringstudies en produksieprestasie studie is uitgevoer. In die eerste twee studies is die skynbare stikstof (AND)- en aminosuur (AAD) verteringskoöeffisiënte bepaal deur gebruik te maak van digesta wat by die terminale ileum ingesamel is (ileale verteringsmetode). In die derde studie is die produksie prestasie van braaikuikens op ‘n gebalanseerde metaboliseerbare energie (AME) rantsoen, soos beïnvloed deur die verskillende behandelings, geëvalueer. In die eerste studie is knoffel en ‘n kommersiële prebiotikum (Bio-Mos®) geëvalueer en met ‘n antibiotikum (doksisiklien, Doxyveto-SOS) in terme van AND en AAD vergelyk. Beginner- en afrondingsrantsoene is as ‘n meel of pille gevoer. Die knoffel is teen 8g/kg, 13g/kg en 18g/kg in die rantsoen ingesluit. Bio-Mos® is teen 1g/kg, 2g/kg en 3g/kg in die beginner rantsoen en teen 0.5g/kg, 1g/kg en 1.5g/kg in die afrondingsrantsoen, ingesluit. Die antibiotikum is teen 0.3g/kg in beide rantsoene ingesluit. Geen van die behandelings het enige positiewe invloed op AND gehad nie. Deur ‘n verpilde rantsoen te voer het sekere negatiewe invloed op AND gehad. Oor die algemeen het geen behandelings enige positiewe invloed op AAD gehad nie. Op dag 21 en 35 het die insluiting van knoffel teen 18g/kg in ’n meel rantsoen ’n negatiewe invloed op AAD gehad, wanneer dit met die negatiewe- en positiewe kontroles vergelyk is. Dit blyk nie dat om ‘n pil of meel te voer enige invloed op die invloede van die verskillende behandelings gehad het nie. In die tweede studie is Bio-Mos®, ‘n organiese suur (Acid-Pak 4-way®) en ‘n medium-ketting trigliseried (MCT) geëvalueer en met ‘n antbiotikum, doksisiklien (Doxyveto-SOS) in terme van AND en AAD, vergelyk. Beginner- en afrondingsrantsoene is gevoer as ‘n meel. Bio-Mos® is teen 1g/kg, 2g/kg, and 3g/kg in die beginner rantsoen en teen 0.5g/kg, 1g/kg, 1.5g/kg in die afrondingsrantsoen, ingesluit. Acid-Pak 4-way® is teen 0.4g/kg, 1g/kg en 1.6g/kg vir die beginner –en afrondingsrantsoene ingesluit. Die MCT is teen 3g/kg, 3.6g/kg, 4.2g/kg in die beginner rantsoen en teen 2.1g/kg, 2.7g/kg en 3.4g/kg in die afrondingsrantsoen ingesluit. Die antibiotikum is ingesluit teen 0.3g/kg. Geen behandelings het enige betekenisvolle invloed in terme van AND gehad nie. Op dag 21 het MCT (3.4g/kg), in vergelyking met die negatiewe- en positiewe kontrole, die grootste positiewe invloed op AAD gehad. Acid-Pak 4-way® (1g/kg) het, in vergelyking met die positiewe kontrole, ‘n positiewe invloed gehad op AAD. Op dag 28, het Bio-Mos® (0.5g/kg en 1.5g/kg) en Acid-Pak 4-way® (0.4g/kg) die grootste positiewe invloed op AAD gehad. Die behandeling met MCT (2.7g/kg) het die mees negatiewe invloed op AAD gehad. In die derde studie is die insluiting van Bio-Mos®, Acid-Pak 4-way® en MCT getoets om die invloed op braaikuiken produksie prestasie te evalueer, en te vergelyk met die invloed van die insluiting of afwesigheid van ‘n antibiotikum. Liggaamsmassa (BW), liggaamsmassa toename (BWG), voerinname (FI) en voeromsetverhouding (FCR) is gemeet. Beginner- en afrondings rantsoene is gevoer as ‘n meel. Bio-Mos®, MCT en Acid-Pak 4-way® is onderskeidelik teen 3.0g/kg, 4,2g/kg en 1.6g/kg in die rantsoen ingesluit. Die kuikens is met aankoms (per hok) geweeg, asook op dae 7, 14, 21, 28, 35. Voerinname per hok is gemeet op dae 7, 14, 21, 28 en 35. Mortaliteite is daagliks aangeteken. Die insluiting van Acid-Pak 4-way® het in vergelyking met die negatiewe kontrole, Bio-Mos® en MCT insluiting ‘n hoër BWG tot gevolg gehad. Die gevolgtrekking wat gemaak kan word is dat Bio-Mos®, Acid-Pak 4-way® en MCT gebruik kan word as ‘n moontlike alternatief vir antibiotika insluiting. Hierdie drie behandelings was nie noodwending meer effektief as die antibiotika nie, maar het wel bewys dat dit kompeterende alternatiewe is.

Introdução: Os efeitos metabólicos do uso combinado dos triglicerídeos de cadeia média (TCM) e do óleo de peixe (OP) na esteatose hepática ainda não estão totalmente esclarecidos. Objetivo: O presente estudo teve o objetivo de verificar os efeitos da combinação dos TCMs e OP na esteatose hepática e estresse oxidativo induzidos pela dieta hiperlipídica (HL+) termolizada em ratos. Material e Métodos: Foram utilizados no total 50 ratos machos da linhagem Wistar. O grupo Controle (n=10) recebeu a dieta controle. Os grupos HL+ receberam a dieta contendo 50% de gordura animal (GA) termolizada e 50% de ração. A adaptação às dietas HL+ foi realizada durante 5 dias. Os grupos HL+GA, HL+TCM, HL+OP e HL+TCM/OP (n=10) receberam a dieta HL+ com 50% de lipídios (gordura animal termolizada) durante 30 dias. Após este período, os grupos HL+TCM, HL+OP e HL+OP/TCM receberam as dietas HL+ adicionadas de óleo de TCM (OTCM), OP e OTCM + OP, respectivamente, durante 20 dias. As análises realizadas foram a gordura hepática total, frações lipídicas hepáticas e séricas, glicemia, vitamina E e retinol séricos, glutationa reduzida (GSH) e malondialdeído (MDA) sérico e hepático e aminotransferases séricas. Resultados: Os grupos HL+ apresentaram acúmulo significativo de gordura total e triglicerídeos hepáticos, exceto o HL+OP. Apenas o grupo HL+TCM não apresentou acúmulo significativo de colesterol total hepático (CT). Este mesmo grupo apresentou valores maiores de CT e HDLcol séricos e menor razão triglicerídeos/HDLcol. Os valores séricos de aminotransferases foram significativamente maiores nos grupos que receberam os OTCM e/ou OP. A peroxidação lipídica (LPO) hepática foi maior foi nos grupos HL+, exceto o HL+TCM. Apenas o grupo HL+GA apresentou maior LPO sérica. Verificou-se que a GSH foi maior nos grupos HL+GA, HL+TCM e HL+OP/TCM, a vitamina E sérica foi menor nos grupos HL+GA, HL+OP e HL+OP/TCM e o retinol sérico foi maior nos grupos HL+GA e HL+TCM. Conclusões: As alterações séricas não refletiram as alterações hepáticas em relação aos lipídios, estresse oxidativo e antioxidantes. O uso do óleo de TCM e óleo de peixe em associação na dieta HL+ resultou em efeito negativo devido ao maior acúmulo de gordura hepática tanto na forma de triglicerídeos quanto de colesterol, maior peroxidação lipídica hepática e menor vitamina E sérica. / Introduction: The metabolic effects of combined use of medium chain triglycerides (MCT) and fish oil (FO) on non alcoholic hepatic steatosis are not fully understood. Objective: The aim of this study was to investigate the effects of the combination of MCT and FO on hepatic steatosis and oxidative stress induced by high fat (HF+) thermolyzed diet in rats. Methodology: Fifty wistar male rats were studied. The Control group (n = 10) received the standard diet. The HF+ groups received diet with 50% of thermolyzed animal fat (AF) and 50% of ration. Five days were dedicated for adaptation to high-fat diets. The groups HF+AF, HF+MCT, HF+FO and HF+MCT/FO (n = 10) received HF+ diet with 50% thermolyzed fat during 30 days. After this period, the groups HF+MCT, HF+FO and HF+MCT/FO received HF+ diets with MCT oil (MCTO), FO and MCTO + OP, respectively, during 20 days. Analysis of total liver fat, liver and serum lipid fractions, serum glucose, vitamin E and retinol, serum and liver reduced glutathione (GSH) and malondialdehyde (MDA), and serum aminotransferases (AST and ALT) were performed. Results: The groups HF+ showed higher total fat and triglycerides, except HF+FO. Only HF+MCT group didn´t have higher liver total colesterol (TC). This same group had higher serum TC and HDLcol and lower triglycerides/HDLcol ratio. The groups fed with MCTO and/or FO had higher serum aminotransferase. Liver lipid peroxidation (LPO) was higher in HF+ groups, except HF+MCT. Serum LPO was higher in HF+AF. The hepatic GSH was higher in the groups HF+AF, HF+MCT and HF+MCT/FO, serum vitamin E was lower in groups HF+AF, HF+FO and HF+MCT/FO, and serum retinol was higher in groups HF+AF and HF+MCT. Conclusions: Lipids, oxidative stress and antioxidant serum and liver alterations didnt correspond. The association of MCTO with FO in HF+ diet resulted in a negative effect when it concerns liver fat, triglyceride and cholesterol accumulation, higher liver lipid peroxidation and lower serum vitamin E.