The primary purpose of this study was to test the predictions of the Dual-mode theory using arm ergometry as the exercise modality. It was hypothesized that changes in affect during exercise would be greater in high (105% GET) and low (80% GET) intensity exercise conditions than in a control condition, while differences in affect would be observed between exercise conditions. In addition, it was predicted that during recovery, there would be no differences in affect between the exercise conditions. Study participants were 24 physically active men. A within-subjects design was used. Affect was measured using the Activation-Deactivation Adjective Check List (Thayer, 1986) and the State Anxiety Inventory (Spielberger et al., 1970). Cognitive (i.e., self-efficacy, enjoyment) and physiological (i.e., heart rate, pain, perceived exertion) mediators of the exercise-affect relationship were also examined. Results showed that during exercise, changes in affect were greater in the exercise conditions than the control condition, and affective valence in the exercise conditions declined relative to the control condition. In partial support of the Dual-mode theory, self-efficacy mediated the relationship between below GET exercise and affect, whereas pain mediated the relationship between above GET exercise and affect. During recovery, arousal was higher in the exercise conditions compared to control, affective valence was less positive compared to control, and state anxiety did not differ across conditions. Finally, there were no significant differences between the two exercise conditions on any of the affect measures. These findings highlight the importance of exercise intensity to the affective benefits of exercise. / Thesis / Master of Arts (MA)

This study investigated the effects of peristaltic pulse dynamic compression (PPDC) on range-of-motion (ROM) changes in forward splits. Serious stretching usually involves discomfort and large time investments. Tissue structural changes and stretch tolerance have heretofore been considered the primary mechanisms of enhanced ROM. The PPDC treatment was computer controlled. Circumferential and segmented inflation pressures were induced by feet to hip leggings. Nine subjects, experienced in stretching and a forward split position, volunteered. The subjects were familiarized with the protocol and randomly assigned to an initial condition: experimental (PPDC), or control (CONT). The study involved a crossover design. Second conditions were tested within 1–5 days. All tests were 2 trials of right and left forward splits. Split flexibility was assessed by measuring the height of the anterior superior iliac spine of the rear leg from the floor. Pelvic posture was controlled by rear leg position. The PPDC treatment was 15 minutes of seated PPDC. The control condition was the same except that leggings were not inflated. Pressures of 5 cells in the leggings were set at factory defaults, 70 mm Hg sequentially. Difference score results indicated statistically significant (p ≤ 0.05) differences by condition and the condition by leg interaction. The rapid acute changes in ROM (PPDC: right 25.3%, left 33.3%; CONT: right 12.2%, left 1.0%) support the premise that changes in ROM were dependent on mechanisms other than tissue structural changes and/or stretch tolerance. PPDC provides a means of rapidly enhancing acute ROM requiring less discomfort and time.

The mechanisms underlying caffeine’s acute effects and withdrawal symptoms are not entirely understood. The purpose was to determine whether these effects or symptoms co-exist in clusters, and whether they are associated with polymorphisms in β1- and β2-adrenoceptors. Subjects (n=1271) were from the Toronto Nutrigenomics and Health Study. The acute effects and withdrawal symptoms clustered into 4 and 6 factors, respectively. Subjects with the ADRβ2 Gly16Arg Gly/Arg genotype were more likely than Gly allele homozygotes to report “fatigue” withdrawal symptoms. Among >200 mg/d caffeine consumers, ADRβ2 Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting ‘flu-like somatic’ withdrawal symptoms. Among subjects with the CYP1A2 -163 A>C A/A genotype and 100-200 mg/d caffeine consumers, ADRβ1 Arg389Gly Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting “dysphoric mood” withdrawal symptoms. The findings suggest that β1- and β2- adrenoceptors play a role in caffeine withdrawal.

The mechanisms underlying caffeine’s acute effects and withdrawal symptoms are not entirely understood. The purpose was to determine whether these effects or symptoms co-exist in clusters, and whether they are associated with polymorphisms in β1- and β2-adrenoceptors. Subjects (n=1271) were from the Toronto Nutrigenomics and Health Study. The acute effects and withdrawal symptoms clustered into 4 and 6 factors, respectively. Subjects with the ADRβ2 Gly16Arg Gly/Arg genotype were more likely than Gly allele homozygotes to report “fatigue” withdrawal symptoms. Among >200 mg/d caffeine consumers, ADRβ2 Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting ‘flu-like somatic’ withdrawal symptoms. Among subjects with the CYP1A2 -163 A>C A/A genotype and 100-200 mg/d caffeine consumers, ADRβ1 Arg389Gly Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting “dysphoric mood” withdrawal symptoms. The findings suggest that β1- and β2- adrenoceptors play a role in caffeine withdrawal.

O Estado do Tocantins está se tornando um dos principais polos de cultivo agrícola do Brasil e a disponibilidade de recursos hídricos têm fortalecido a produção agrícola no Estado. As áreas de monocultura estendem-se principalmente ao longo da bacia hidrográfica Araguaia e Tocantins, sendo estes os dois principais sistemas de drenagem. Para obtenção de elevadas produtividades, os cultivos agrícolas são altamente dependentes do uso de pesticidas. Adicionalmente, os pesticidas agrícolas podem chegar aos ecossistemas aquáticos através da lixiviação e deriva após a aplicação e também através da adsorção a materiais biológicos e às partículas de argila do solo que são carregados para sistemas aquáticos pelos processos de erosão. Consequentemente, o ecossistema aquático pode ser afetado, devido ao efeito tóxico destes pesticidas para espécies aquáticas de diferentes níveis tróficos. Como resultado de uma pesquisa de campo em várias áreas de cultivo no Estado do Tocantins, verificou-se que o inseticida tiametoxam (TMX), o fungicida ciproconazol (CPZ) e o herbicida Paraquat (PQ) estão entre os principais pesticidas utilizados em diversas culturas e em diferentes áreas de cultivo. O objetivo deste estudo foi avaliar a toxicidade de TMX, CPZ e PQ para invertebrados de água doce, de modo a contribuir para análise de risco ecológico de pesticidas agrícolas no ecossistema da bacia hidrográfica Araguaia-Tocantins. Como a informação sobre a toxicidade letal e sub-letal de diferentes compostos, particularmente para espécies aquáticas ecologicamente relevantes, é crucial para a avaliação dos riscos de pesticidas em ecossistemas aquáticos, foram realizados ensaios ecotoxicológicos, utilizando ensaios laboratoriais com dois invertebrados de água doce, o díptero Chironomus riparius e a planária Dugesia tigrina. Estudos preliminares revelaram que TMX não é tóxico para D. tigrina em concentrações ambientalmente relevantes, logo a toxicidade deste pesticida foi avaliada apenas sobre C. riparius (sobrevivência, crescimento, emergência e avaliação de respostas bioquímicas). Na avaliação da toxicidade de CPZ, os parâmetros avaliados em C. riparius incluem sobrevivência, crescimento e emergência, enquanto que em D. tigrina foram avaliados sobrevivência, regeneração e respostas comportamentais (locomoção e alimentação). Para avaliação da toxicidade de PQ, ensaios crônicos foram conduzidos com C. riparius (avaliação de crescimento, emergência e peso de mosquitos adultos) e D. tigrina (avaliação de regeneração, locomoção e alimentação). Os resultados evidenciaram que TMX é altamente tóxico para C. riparius, uma vez que concentrações ambientalmente relevantes afetam não só o desenvolvimento do organismo, mas também a sobrevivência. O fungicida CPZ é moderadamente tóxico para C. riparius (atraso no tempo à emergência) e D. tigrina (decréscimo da atividade locomotora, atividade alimentar e capacidade de regeneração). O herbicida PQ também provocou atraso no tempo à emergência, além de diminuição do tamanho dos adultos de C. riparius, bem como redução na atividade locomotora, atividade alimentar e capacidade de regeneração de D. tigrina. Este estudo acrescenta dados ecotoxicológicos sobre os efeitos de TMX, CPZ e PQ sobre invertebrados de água doce e sugere que, em longo prazo, estes pesticidas podem potencialmente perturbar cadeias alimentares e estrutura da comunidade nos ecossistemas de água doce. A aplicação destes pesticidas em particular na bacia hidrográfica Araguaia-Tocantins deve ser cuidadosamente monitorada nas áreas agrícolas de modo evitar impactos sobre os ecossistemas aquáticos. / The State of Tocantins is becoming one of the main agricultural centers in Brazil, and the availability of water resources have strengthened agricultural production in the state. Monoculture areas extend mainly along the Araguaia and Tocantins watersheds, which are the two main drainage systems. To achieve high productivity, agricultural crops are highly dependent of pesticide use. As such, agricultural pesticides may reach the aquatic ecosystems through leaching and drift after application, also through the adsorption to biological materials and soil clay particles that are carried to aquatic system by erosion. Consequently, the aquatic ecosystem may be affected due to the toxic effect of these pesticides to aquatic species of different trophic levels. As a result of a field survey of several areas of cultivation in the State of Tocantins, it was found that the insecticide thiamethoxam (TMX), the fungicide cyproconazole (CPZ) and the herbicide paraquat (PQ) are the main pesticides used in many crops, in different areas of cultivation. The aim of this study was to evaluate the toxicity of TMX, CPZ and PQ for freshwater invertebrates, in order to contribute to ecological risk assessment of agricultural pesticides in the ecosystem of the Araguaia-Tocantins watershed. Since information on the lethal and sub-lethal toxicity of the different compounds, particularly for ecologically relevant aquatic species, is crucial for risk assessment of pesticide in aquatic ecosystems, ecotoxicological tests were carried using laboratory tests with two freshwater invertebrates, the dipteran Chironomus riparius and the planarian Dugesia tigrina. Preliminary studies revealed that environmentally relevant concentrations of TMX is did not induced toxicity to D. tigrina and thus, effects of this insecticide were evaluated only using C. riparius (survival, growth, emergence and evaluation of biochemical responses). In the evaluation of CPZ toxicity, the endpoints evaluated in C. riparius included survival, growth and emergence, while in D. tigrina effects were evaluated in terms of survival, regeneration and behavioral responses (locomotion and feeding). For the assessment of PQ toxicity, chronic tests were conducted with C. riparius (growth, emergence and adult weight) and D. tigrina (regeneration, locomotion, and feeding). Our results showed that TMX is highly toxic to C. riparius, since environmentally relevant concentrations affects not only the development rates, but also survival. The CPZ fungicide is moderately toxic to C. riparius (delayed emergence time) and D. tigrina (decreased locomotor activity, feeding activity and delayed regeneration). The herbicide PQ also caused a delay in emergence time and decrease in body weight of C. riparius imagos, as well as reduction in locomotor activity, feeding activity and regeneration of D. tigrina. This study adds ecotoxicological data on the effects of TMX, CPZ and PQ to freshwater invertebrates and suggests that in the long term, these pesticides can potentially disrupt food chains and community structure in freshwater ecosystems. The application of these pesticides namely in the Araguaia-Tocantins watershed should thus be closely monitored in agricultural areas in order to avoid impacts on aquatic ecosystems.

Synthetic N-methoxybenzyl ("NBOMe") phenylethylamine derivatives were developed as highly potent agonists for the research of 5-hydroxytryptamine receptors, however they have become available on the black market in the past few years. They are sought by recreational users as "legal LSD", in worse cases the replacement is unsuspected and these substances are a cause of serious intoxication with signs of serotonin toxicity. At this moment, there is very little data available, but their low price, easy access via the internet and legal status make these substances an interesting target for recreational users and a big challenge for scientists and for the lawmakers. 2CBFly-NBOMe belongs to this group. There is no information about its recreational use for now, but thiat is probably only a matter of time. The aim of this study is to determine acute effects of 2CBFly-NBOMe in Wistar rats. Active substance significantly reduced locomotor activity of the animals and caused higher anxiety, it also disrupted sensorimotor gating and lowered body temperature of animals. Pharmacokinetic profile was measured only in the blood serum, the highest concentrations of 2CBFly-NBOMe were detected 30-60 minutes after the administration of hallucinogen. This paper provides first information on the effect of 2CBFly-NBOMe on...

Multiple Sklerose (MS) ist eine chronisch-entzündliche Erkrankung des Zentralen Nervensystems. Die Bedeutung der B-Zellen bei der MS-Pathogenese ist in den letzten Jahren zunehmend in den Vordergrund gerückt. Das Wirkprinzip des humanisierten monoklonalen Antikörpers Ocrelizumab beruht auf der selektiven Depletion CD20-exprimierender B-Zellen. Ocrelizumab ist seit 2018 für die schubförmig remittierende und primär progrediente Verlaufsform der MS zugelassen. Bisher ist wenig über die Medikamenteneffekte unmittelbar nach den Infusionen bekannt. Das Ziel dieser Arbeit ist die Untersuchung der akuten Veränderungen von immunologischen und Routine-Laborparametern und deren klinische Relevanz in Gegenüberstellung zu den langfristigen Veränderungen. Wir überwachten die infusionsassoziierten Reaktionen und die Vitalparameter Temperatur, Blutdruck und Herzfrequenz von 68 MS-Patientinnen und Patienten (Pat.) während der Ocrelizumab-Infusionen im ersten Behandlungsjahr. Es wurden jeweils Routine-Laborparameter wie Blutbild, Leberenzyme, Nierenfunktion, Akute-Phase-Proteine und die Komplementaktivierung erhoben und eine umfangreiche durchflusszytometrische Analyse der peripheren Immunzellen vor und nach der Prämedikation mit Methylprednisolon und nach der Ocrelizumab-Gabe durchgeführt. Darüber hinaus wurden zu jedem Untersuchungszeitpunkt 13 Serumzytokine mittels eines Bead-basierten Assays quantifiziert. In unserer Studie traten vorwiegend milde infusionsassoziierte Reaktionen am häufigsten im Rahmen der ersten Infusion (35 %) auf. Zwei Pat. erlitten eine akute Überempfindlichkeitsreaktion. Die Vitalparameter veränderten sich während der Infusionen nicht signifikant. Die pro-inflammatorischen Serumzytokine IL-6 und TNF-α stiegen nach der ersten Infusion deutlich an. Auch IL-1ß, IL-4, IL-12, IL-17A und IFN-ɣ wiesen bei den ersten Infusionen höhere Konzentrationen auf als im Verlauf. Eine direkte Korrelation zwischen den Zytokinanstiegen und der klinischen Symptomatik ließ sich nicht herstellen. Leber- und Nierenwerte wurden durch die Ocrelizumab-Therapie nicht signifikant beeinflusst, ebenso wie die Akute-Phase-Proteine CRP und PCT. Unmittelbar nach den Infusionen stiegen die Leukozyten und neutrophilen Granulozyten jeweils an, während die eosinophilen und basophilen Granulozyten und die Monozyten abfielen. Langfristig blieben diese Zellzahlen jedoch stabil. Weitere Zellen des angeborenen Immunsystems wie die natürlichen Killerzellen und die dendritischen Zellen zeigten unspezifische Veränderungen. Obwohl in unserer Studienpopulation nur von wenigen und leichten Infektionen berichtet wurde, wiesen 80 % der Pat. nach der ersten Medikamentengabe eine Lymphopenie auf. Allerdings war die Lymphozytenzahl unserer Pat. im Durchschnitt bereits zu Beginn der Therapie niedrig. Zwischen den Infusionszyklen beobachteten wir eine Erholung der Lymphozyten. Aufgrund des Wirkmechanismus von Ocrelizumab fiel die durchschnittliche B-Zellzahl nach der ersten Infusion auf Werte nahe 0 Gpt/l. Auch alle anderen CD20-positiven B-Zellsubpopulationen wurden sofort depletiert. Unter fortlaufender Therapie blieb die B-Zellzahl weiterhin sehr gering, die Zusammensetzung des BZ-Kompartiments änderte sich im Therapieverlauf aber nicht. Die Zahl der zirkulierenden T-Zellen nahm bei jedem Infusionszyklus ebenfalls signifikant ab. Funktionelle Veränderungen in weiteren untersuchten T-Zellpopulationen fanden sich nicht, die T-Zell-Zusammensetzung blieb stabil. Die T-Zellen erholten sich zwischen den Infusionszyklen, langfristig kam es nicht zu einer Abnahme der Zellzahl. Wie wir zeigen konnten, führt die Therapie mit Ocrelizumab zu einem unmittelbaren Eingriff in das Immunsystem. Die Zusammensetzung der Immunkompartimente bleibt dabei weitestgehend erhalten, von einer dauerhaften zellulären Immunsuppression ist basierend auf unseren immunologischen und klinischen Ergebnissen nicht auszugehen. Die zellulären Veränderungen sind bei der Überwachung der Routine-Laborparameter und der Lymphozytensubpopulationen zu beachten, während die Akute-Phase-Proteine weiterhin zuverlässige Aussagen liefern. Die infusionsassoziierten Reaktionen fallen moderat aus, möglicherweise liegt ihnen der mäßig ausfallende Zytokinanstieg zugrunde. Da die Vitalparameter die infusionsassoziierten Reaktionen nicht zuverlässig anzeigen konnten, empfehlen wir in erster Linie eine klinische Überwachung der Patienten.:Inhaltsverzeichnis III Tabellenverzeichnis V Abbildungsverzeichnis VI Abkürzungsverzeichnis IX 1. Einleitung 1 1.1 Multiple Sklerose: Definition und Epidemiologie 1 1.2 Ätiologie 2 1.3 Immunpathogenese 2 1.3.1 Angeborene Immunabwehr 3 1.3.2 Erworbene Immunabwehr 5 1.4 Klinik 8 1.5 Diagnostik 10 1.6 Therapie 13 1.6.1 Schubtherapie 13 1.6.2 Verlaufsmodifizierende Therapie 13 1.6.3 Symptomatische Therapie 18 2. Zielsetzung 19 3. Material und Methoden 21 3.1 Material 21 3.1.1 Chemikalien 21 3.1.2 Grundmedien und Medienzusätze 21 3.1.3 Lösungen und Puffer 22 3.1.4 Antikörper 22 3.1.5 Sonstige Materialien 24 3.1.6 Geräte 25 3.2 Methoden 26 3.2.1 Patientinnen und Patienten 26 3.2.2 Medikamentengabe 26 3.2.3 Infusionsassoziierte Reaktionen und Vitalwerte 27 3.2.4 Blutuntersuchungen 27 3.2.5 Statistische Auswertung 31 4. Ergebnisse 33 4.1 Patientinnen- und Patientencharakteristika 33 4.2 Infusionsassoziierte Reaktionen, Nebenwirkungen und Infektionen 34 4.3 Vitalparameter während der Infusion 35 4.4 Routine-Laborparameter 36 4.4.1 Blutbild 36 4.4.2 Klinische Chemie 40 4.4.3 Akute-Phase-Proteine 42 4.4.4 Komplement und LDH 43 4.4.5 Immunstatus und Lymphozyten-Subtypisierung 45 4.5 Immunphänotypisierung mittels Durchflusszytometrie 47 4.5.1 B-Zellen 48 4.5.2 T-Zellen 52 4.5.3 Natürliche Killerzellen 58 4.5.4 Monozyten 60 4.5.5 Dendritische Zellen 62 4.6 Apoptose 65 4.6.1 B-Zellen 65 4.6.2 T-Zellen 66 4.6.3 Weitere Zelltypen 67 4.7 Zytokine 67 4.7.1 Pro-inflammatorische Zytokine 68 4.7.2 Anti-inflammatorische Zytokine 71 4.7.3 T-Zell-spezifische Zytokine 72 5. Diskussion 75 6. Zusammenfassung 87 7. Summary 89 Literaturverzeichnis XI Anlage 1 XXVIII Anlage 2 XXIX / Multiple sclerosis is a chronic inflammatory disease of the central nervous system. The role of B cells in the pathogenesis of multiple sclerosis has increasingly come to the fore in recent years. Ocrelizumab, a humanized monoclonal antibody, selectively depletes CD20-expressing B cells. The drug was approved for the relapsing-remitting and primary progressive forms of multiple sclerosis in 2018. Up to now, little is known about the effects immediately following the infusion of ocrelizumab. The aim of this study was to investigate acute changes in immunologic and routine laboratory parameters and their clinical relevance in comparison to long-term changes. Therefore, we monitored infusion-associated reactions and the vital signs temperature, blood pressure, and heart rate of 68 multiple sclerosis patients during ocrelizumab infusion in the first year of treatment. Routine laboratory parameters such as blood count, liver enzymes, renal function, acute phase proteins, and complement activation were measured. Additionally, a detailed flow cytometric analysis of peripheral immune cells was performed before and after premedication with methylprednisolone and after ocrelizumab administration. At each time point, 13 serum cytokines were quantified using a bead-based assay. In our study, infusion-associated reactions were mainly mild and occurred most frequently (35 %) during the first administration of ocrelizumab. Two patients suffered from an acute hypersensitivity reaction. There were no relevant changes in vital signs. Proinflammatory serum cytokine levels of IL-6 and TNF-α clearly rose after the first ocrelizumab infusion. The levels of IL-1ß, IL-4, IL-12, IL-17A and IFN-ɣ were also detected higher after the first few infusions compared to follow up. However, serum cytokine levels of our patients did not directly correlate with clinical symptoms. Liver enzymes and kidney function remained stable. Neither immediately after infusion nor in the course of ocrelizumab therapy, the acute-phase proteins CRP and PCT were significantly affected. Leukocytes and neutrophil granulocytes rose immediately after each infusion, while eosinophil and basophil granulocytes and monocytes decreased. In the long term, these parameters remained stable. Natural killer cells and dendritic cells showed nonspecific changes. Although infrequent and only mild infections were reported in our study population, 80 % of our patients presented lymphopenia after the first ocrelizumab administration. The lymphocyte count of our patients was already low on average at the start of therapy. Between infusion cycles, we mostly observed a recovery of the lymphocyte count. Due to the mechanism of action of ocrelizumab, B cells dropped close to 0 Gpt/l after the first infusion and remained very low. All observed CD20+ B cell subpopulations showed similar behaviour and the constitution of the B cell compartment did not change over time. Circulating T cells also decreased significantly with each infusion cycle. However, T cells recovered between infusion cycles and no long-term decrease in cell number could be detected. We could not report on functional changes in T cell subpopulations and the constitution of T cell compartment remained stable over time. In summary, ocrelizumab therapy leads to a significant change in the immune system. The constitution of the immune compartments is mostly preserved. Based on our immunological and clinical results, a relevant cellular immunosuppression cannot be assumed. Cellular changes with ocrelizumab therapy need to be considered during monitoring of routine laboratory parameters and lymphocyte subpopulations, while acute-phase proteins can continue to provide reliable predictions. Ocrelizumab leads only to mild infusion-associated reactions. These reactions could be due to cytokine release, as a moderate increase in serum cytokine levels could be measured. Since vital signs did not reliably reflect infusion-related reactions, we mainly recommend to focus on clinical monitoring.:Inhaltsverzeichnis III Tabellenverzeichnis V Abbildungsverzeichnis VI Abkürzungsverzeichnis IX 1. Einleitung 1 1.1 Multiple Sklerose: Definition und Epidemiologie 1 1.2 Ätiologie 2 1.3 Immunpathogenese 2 1.3.1 Angeborene Immunabwehr 3 1.3.2 Erworbene Immunabwehr 5 1.4 Klinik 8 1.5 Diagnostik 10 1.6 Therapie 13 1.6.1 Schubtherapie 13 1.6.2 Verlaufsmodifizierende Therapie 13 1.6.3 Symptomatische Therapie 18 2. Zielsetzung 19 3. Material und Methoden 21 3.1 Material 21 3.1.1 Chemikalien 21 3.1.2 Grundmedien und Medienzusätze 21 3.1.3 Lösungen und Puffer 22 3.1.4 Antikörper 22 3.1.5 Sonstige Materialien 24 3.1.6 Geräte 25 3.2 Methoden 26 3.2.1 Patientinnen und Patienten 26 3.2.2 Medikamentengabe 26 3.2.3 Infusionsassoziierte Reaktionen und Vitalwerte 27 3.2.4 Blutuntersuchungen 27 3.2.5 Statistische Auswertung 31 4. Ergebnisse 33 4.1 Patientinnen- und Patientencharakteristika 33 4.2 Infusionsassoziierte Reaktionen, Nebenwirkungen und Infektionen 34 4.3 Vitalparameter während der Infusion 35 4.4 Routine-Laborparameter 36 4.4.1 Blutbild 36 4.4.2 Klinische Chemie 40 4.4.3 Akute-Phase-Proteine 42 4.4.4 Komplement und LDH 43 4.4.5 Immunstatus und Lymphozyten-Subtypisierung 45 4.5 Immunphänotypisierung mittels Durchflusszytometrie 47 4.5.1 B-Zellen 48 4.5.2 T-Zellen 52 4.5.3 Natürliche Killerzellen 58 4.5.4 Monozyten 60 4.5.5 Dendritische Zellen 62 4.6 Apoptose 65 4.6.1 B-Zellen 65 4.6.2 T-Zellen 66 4.6.3 Weitere Zelltypen 67 4.7 Zytokine 67 4.7.1 Pro-inflammatorische Zytokine 68 4.7.2 Anti-inflammatorische Zytokine 71 4.7.3 T-Zell-spezifische Zytokine 72 5. Diskussion 75 6. Zusammenfassung 87 7. Summary 89 Literaturverzeichnis XI Anlage 1 XXVIII Anlage 2 XXIX

Made available in DSpace on 2016-06-02T19:22:50Z (GMT). No. of bitstreams: 1 2189.pdf: 840243 bytes, checksum: df5c31ed96eff502c06d8ea77cffe86d (MD5) Previous issue date: 2008-06-27 / Financiadora de Estudos e Projetos / The inability to oxidize fat is a key factor in the etiology of obesity. However, improved performance and VO2max resulting from physical training leads to increased rates of oxidation of fats. Although, there is still a lack of information about the intensity of exercise can interfere with metabolism of carbohydrates and lipids in obese women during a session of exercise and its recovery, because only in an experimental study there is a negative relationship of obesity on the reinstatement of power after a year. Therefore, this study aims to assess the behavior of the metabolism of carbohydrates and lipids in moderately obese women on a test of acute exercise effects on the intensity of ventilatory threshold and the recovery period, in the stage of pre-and post-training physical. This study had the participation of seven women slightly obese (BMI=4.03 kg/m2), with an average age of 43.0 ± 4.0 years, 163 ± 0.2±33.59 cm and previously sedentary who were submitted to the ergospirometry acute test before and after 16 weeks of training in the intensity of ventilatory threshold. During the test respiratory quotient was evaluated to determine the fats and carbohydrates oxidation during exercise and recovery period. The results found that the volunteers used predominantly the energy that comes from carbohydrates during the session of exercise (67.64% and 69.35% of the total spent provided pre-and post-training, respectively). During recovery the percentage of the fats contribution increase of (46.52% of the total oxidized) to the total energy generated, which discreetly marked with training (53.48% of the total oxidized). Based on the findings was observed that the metabolism of carbohydrates provides the muscle contraction support during the exercise in the intensity of ventilatory threshold and that the recovery period lipid metabolism is the counterpart to repay the body stores energy in obese women. / A inabilidade de oxidar gorduras é um fator chave na etiologia da obesidade. No entanto, a melhoria de performance e do VO2max advinda do treinamento físico leva a um aumento das taxas de oxidação de gorduras. Porém, ainda faltam esclarecimentos sobre como a intensidade do exercício pode interferir no metabolismo de carboidratos e de lipídeos de mulheres obesas durante uma sessão de exercício e a sua recuperação, já que apenas em estudo experimental observa-se a relação negativa da obesidade sobre a reposição da energia após um exercício. Sendo assim, o objetivo do presente estudo é de verificar o comportamento do metabolismo de carboidratos e de lipídeos de mulheres moderadamente obesas sobre efeito de um teste agudo de exercício na intensidade do limiar ventilatório e o seu período de recuperação, na condição pré e pós-treinamento físico. Para tanto, o estudo contou com a participação de sete mulheres levemente obesas (IMC=33,59 ± 4,03 Kg/m2), com média de idade de 43,0 ± 4,0 anos, 163 ± 0,2 cm e previamente sedentárias que foram submetidas ao teste agudo de ergoespirometria, no inicio e após transcorridas 16 semanas de treinamento na intensidade do limiar ventilatório. Durante o teste foi avaliado o quociente respiratório para determinação da oxidação de gorduras e de carboidratos durante o exercício e o seu período de recuperação. Com base nos resultados obtidos verificou-se que as voluntárias utilizam predominantemente a energia que advém de carboidratos durante a sessão de exercício (67,64 % e 69,35 % do total oxidado na condição pré e pós-treinamento, respectivamente). Durante a recuperação as gorduras aumentam o percentual de contribuição (46,52 % do total oxidado) para o total de energia gerada, condição discretamente acentuada com o treinamento (53,48 % do total oxidado). Com base nos achados acredita-se que o metabolismo de carboidratos oferece suporte para a contração muscular durante o exercício físico na intensidade do limiar ventilatório e que no período de recuperação o metabolismo lipídico faz a contrapartida para reposição dos estoques de energia corporal em mulheres obesas.