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Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser.

Peritoneal dialysis (PD) is a form of renal replacement therapy using the peritoneum as a dialysis membrane. PD solutions employed to remove nitrogen metabolites and excess plasma fluid, and to restore electrolyte and acid-base balance are being developed to minimize local and systemic inflammatory responses while maintaining peritoneal homeostasis and host defense. The effect of chronic action of PD solutions on the peritoneum results in its remodeling and, possibly, eventual loss of peritoneal ultrafiltration capacity. Factors most responsible for late complications and peritoneal remodeling include high glucose levels in PD solutions, and the presence and formation of glucose degradation products (GDP) and advanced glycation end - products (AGEs) in the peritoneal cavity. The aim of our study described in this dissertation was to test various PD solutions with different glucose content and GDP and, using AGEs receptor ligands, to define their systemic effects and identify PD solutions with highest biocompatibility. This part of the dissertation characterizes conventional glucose - based solutions, low - glucose and GDP load solutions as well as glucose polymer (icodextrin) - based PD solutions while determining the plasma and dialysate levels of soluble receptor for AGEs (s - RAGE) and its...

An association between inflammation and mood deterioration has been proposed as a potential explanatory mechanism underlying many pathologies. Previous research attributes this consistently reoccurring connection between inflammation and psychopathology that is often reported within the literature, to a relationship between the HPA axis, the body’s stress response system and the immune system. There is evidence of a bidirectional feedback loop between end-products of the immune system and the HPA-axis such as cytokines and cortisol. This is supported by research reporting that components of subjective well-being such as positive affect, optimism and life satisfaction can produce beneficial health outcomes by potentially targeting this feedback loop. The present longitudinal study tested if higher positive affect independently corresponds to lower levels of inflammatory markers Interleukin-6 (IL-6) and C-reactive protein (CRP) and HPA axis marker cortisol. The study further tested if higher subjective well-being decreases levels of IL-6 and CRP as well as cortisol. The study employed a subsample of participants from the Midlife in Japan (MIDJA) Biomarker project (n=174) that underwent testing at two separate time points across a period of 4 years. The data included subjective well-being, positive affect, IL-6, CRP, cortisol, perceived stress, neuroticism and demographic variables. Positive affect was not associated with any inflammatory marker or cortisol. Subjective well-being had no effect on CRP but reduced IL-6 and cortisol even when controlling for all control and demographic variables. It is concluded that subjective well-being may be linked to lower inflammation and HPA axis activity. / Ett samband mellan inflammation och sjukdomsbeteende har föreslagits som en förklaringsmekanism bakom förekomsten av många patologier. Den konsekventa anknytningen mellan inflammation och psykopatologi som många tidigare studier demonstrerat innebär ett samband mellan immunsystemet och HPA-axeln som är den struktur som utgör kroppens svar på stressorer. Det finns tecken på en återkopplingsslinga mellan slutprodukter av det immunologiska systemet och HPA-axeln såsom cytokiner och kortisol. Detta har stöd i tidigare forskning som rapporterat att komponenter av subjektivt välbefinnande så som positiv affekt, optimism och livstillfredställelse kan medföra positiva hälsoutfall genom att potentiellt influera denna återkopplingsslinga. Förevarande longitudinella studie testar om högre positiv affekt leder till lägre nivåer av de inflammatoriska markörerna interleukin-6 (IL-6) och C-reaktivt protein (CRP) samt HPA-axel markören kortisol. Studien testar vidare även om högre subjektivt välbefinnande leder till lägre nivåer av IL-6, CRP och kortisol. Deltagarna är ett subsampel från Biomarkerprojektet (n = 174) inom Midlife in Japan (MIDJA) som genomgick testning vid två separata tidpunkter över en period av 4 år. Data består av subjektivt välbefinnande, positiv affekt, IL-6, CRP, kortisol, upplevd stress, neuroticism samt demografiska variabler. Positiv affekt hade ingen signifikant effekt på någon av de inflammatoriska markörerna eller kortisol. Subjektivt välbefinnande hade inte någon signifikant effekt på CRP men reducerade signifikant IL-6 och kortisol och dessa effekter förblev signifikanta efter kontroll för samtliga kontroll och demografiska variabler. Följaktligen dras slutsatsen att subjektivt välbefinnande kan leda till lägre inflammation och HPA-axel aktivitet.

SELECTED NUTRIENTS IN ETIOLOGY, PREVENTION AND TREATMENT OF OBESITY The 21st century pandemic of obesity is given by to the obesitogenic environment that helps to develop a positive energy balance, where the energy intake of an individual chronically exceeds his energy need, ie energy expenditure. There is an increase in body weight by increased or abnormal body fat accumulation in the body. Preventing the development of obesity is aimed at achieving energy balance, in the case of existing overweight or obesity, the treatment lies in inducing and maintaining a negative energy balance for some time, ie stimulating energy expenditure and reducing energy intake. Selected diet determines not only energy intake, but its individual nutrients can also partially affect energy expenditure and fat tissue physiology. The aim of this work is to describe and experimentally verify some nutrients that could help in weight reduction and physiological function of adipose tissue. Based on the literature data, 19 active substances or mixtures were considered. A mixture of ω-3 polyunsaturated fatty acids (ω-3 PUFA), eicosapentaenoic acid and docosahexaenoic acid, in a daily dose of 0.6 g, in the form of fish oil in a certified food supplement was chosen as the most suitable for the experiment. In a 12-week, three-arm, parallel...

Peritoneal dialysis (PD) is a form of renal replacement therapy using the peritoneum as a dialysis membrane. PD solutions employed to remove nitrogen metabolites and excess plasma fluid, and to restore electrolyte and acid-base balance are being developed to minimize local and systemic inflammatory responses while maintaining peritoneal homeostasis and host defense. The effect of chronic action of PD solutions on the peritoneum results in its remodeling and, possibly, eventual loss of peritoneal ultrafiltration capacity. Factors most responsible for late complications and peritoneal remodeling include high glucose levels in PD solutions, and the presence and formation of glucose degradation products (GDP) and advanced glycation end - products (AGEs) in the peritoneal cavity. The aim of our study described in this dissertation was to test various PD solutions with different glucose content and GDP and, using AGEs receptor ligands, to define their systemic effects and identify PD solutions with highest biocompatibility. This part of the dissertation characterizes conventional glucose - based solutions, low - glucose and GDP load solutions as well as glucose polymer (icodextrin) - based PD solutions while determining the plasma and dialysate levels of soluble receptor for AGEs (s - RAGE) and its...

Selenoproteine spielen eine wichtige Rolle in der antioxidativen Abwehr und bei Immunreaktionen. Der Selen(Se)metabolismus wird von Hepatozyten gesteuert, die das Se-Transportprotein Selenoprotein P (SEPP) synthetisieren und sezernieren. SEPP nimmt bei kritischen Erkrankungen, z. B. Sepsis ab und führt zu niedrigen Se-Spiegeln. Sepsis triggert die übermäßige Produktion von proinflammatorischen Zytokinen. Aminoglykosid-Antibiotika (AG), die oft bei schwerer Sepsis eingesetzt werden, induzieren Fehlinterpretationen der mRNA inklusive des Stoppcodons UGA welches für die Selenoprotein-Biosynthese notwendig ist. Es wurden daher die molekularen Wechselwirkungen zwischen den Zytokinen IL-6, IL-1b und TNFa, AG und dem Se-Status mit der Biosynthese in Leberzelllinien untersucht. IL-6 führte zu einer starken Reduktion der SEPP-mRNA und einer dosisabhängigen Reduktion von SEPP. Parallel dazu reduzierte IL-6 das Transkriptlevel, die Proteinexpression und die Enzymaktivität der Typ-I-Dejodase (DIO1). Auf die Expression der antioxidativ-wirkenden Glutathionperoxidasen (GPX) wirkte IL-6 isozymspezifisch; während die Transkriptkonzentrationen von GPX2 anstiegen und die von GPX4 abnahmen, blieb GPX1 unbeeinflusst. Die IL-6-abhängigen Effekte bestätigten sich auch in Reportergenassays von SEPP-, DIO1-, GPX2- und GPX4-Promotorkonstrukten. Um die Wirkungen von AG auf die Selenoprotein-Translation besser zu verstehen, wurden die SECIS-Elemente von GPX1-, GPX4- und SEPP-Transkripten in ein Reportersystem kloniert und auf eine Regulation durch AG und Se analysiert. Die Ergebnisse zeigen, dass der korrekte Se-Einbau vom Se-Status, von der AG-Konzentration und dem spezifischen SECIS-Element abhängig ist. Auf transkriptionaler und translationaler Ebene führten AG zu stark erhöhten SEPP-Spiegeln, während die Expression und Enzymaktivität von GPX und DIO1 nur in geringerem Ausmaß beeinflusst wurden. Eine Analyse der Se-Beladung zeigte, dass der Se-Gehalt von SEPP stark durch AG reduziert und vom Se-Status abhängig war. / Selenoproteins play important roles in antioxidant defence and immunoregulation. Selenium (Se) metabolism is controlled by hepatocytes synthesizing and secreting the Se-transporter selenoprotein P (SEPP) declining in critical illness, e.g., sepsis. Sepsis triggers excessive production of pro-inflammatory cytokines. Aminoglycoside (AG) antibiotics applied in sepsis in induce mRNA misinterpretation including the stop codon UGA required during selenoproteins biosynthesis. The molecular interplay between the cytokines IL-6, IL-1b and TNFa, AG and Se-status on selenoprotein expression was investigated in hepatic-derived cell lines. IL-6 strongly reduced the level of SEPP mRNA and secreted SEPP in a dose-dependent manner. Likewise, expression of selenoenzyme type 1 deiodinase (DIO1) declined at the transcript, protein and enzyme activity level. The effects of IL-6 on the expression of antioxidative-acting glutathione peroxidases (GPX) were isozyme-specific; while transcript level of GPX2 increased and those of GPX4 decreased, GPX1 remained unaffected. IL-6-dependent effects were reflected in reporter gene experiments of selenoprotein promoter constructs. Characterising the effects of AG on selenoprotein translation, the SECIS-elements of GPX1, GPX4 and SEPP transcripts were cloned into a reporter system and analysed for their response to AG and Se. The results indicate that the correct co-translational Se-insertion depends on the Se-status, AG concentration and the specific SECIS-element. At both transcriptional and translational levels, SEPP levels were strongly increased in response to AG, whereas the expression and enzyme activity of GPX and DIO1 were affected to a lower degree. Analysis Se-status indicate that the Se-content of SEPP was strongly reduced by AG and depends on Se-status.

No description available.

Prolonged strenuous exercise affects the circulating numbers and functions of immune cells. These effects are thought to be largely mediated by the actions of elevated circulating stress hormones and alterations in regulatory cytokines. Although the effects of a single acute bout of exercise on immune system function are quite well established, it is still not clear how time of day and repeated bouts of prolonged exercise on the same day influence immune function. It is of particular interest to understand the effects of nutritional supplementation on immunoendocrine responses. Therefore, the aims of the studies described in this thesis were to determine the effects of two bouts of prolonged cycling and carbohydrate supplementation on immunoendocrine responses. The saliva collection study showed that the use of a swab for collecting saliva is not an ideal method because it affects the results of saliva composition (Chapter 4). The comparison of the effects of exercise at different times of day on immunoendocrine responses showed that a single bout of prolonged exercise performed in the afternoon induces a larger perturbation in the redistribution of leukocytes into the circulation than an identical bout of morning exercise, which maybe due to higher hypothalamic-pituitaryadrenal (HP A) activation and. circadian rhythms. However, in terms of oral mucosal immunity, performing prolonged cycling at different times of day does not differently affect the salivary responses. The second compared with the first of two bouts of prolonged exercise on the same day induces a greater HP A activation, a larger leukocyte trafficking into the circulation, a decreased neutrophil degranulation response to lipopolysaccharide (LPS) on per cell basis and a lower saliva flow rate, but does not increase plasma interleukin-6 (IL-6), or change saliva immunoglobulin A (slgA) secretion rate (Chapter 5). Furthermore, carbohydrate (CHO) ingestion during any period of two bouts of prolonged exercise shows limited beneficial effect in blunting these higher responses in the second exercise bout compared with the first identical exercise bout on the same day (Chapter 6, 7 and 8). The determination of the effects of CHO ingestion on exercise-induced immunoendocrine responses showed that when two bouts of exercise are performed on the same day, the greater benefit in terms of circulating immunoendocrine responses is obtained by feeding CHO at the earliest opportunity (Chapter 6, 7 and 8). A 3-h interval is insufficient for recovery of leukocyte mobilisation and neutrophil function from the impact of previous exercise whether subjects consumed placebo or CHO during exercise or recovery (Chapter 5, 6, 7 and 8). However, an 18-h interval is sufficient for full recovery of all immunoendocrine variables that were measured in this thesis from the impact of two bouts of prolonged exercise (Chapter 8).

L'homéostasie chlorure (HC) est un acteur essentiel dans la transmission nerveuse. Le GABA, via son récepteur GABAA, permet les mouvements d'ions chlorures en fonction de leur potentiel électrochimique. Dans les neurones sensitifs de ganglions rachidiens dorsaux (GRD), le co-transporteur cation-chlorure NKCC1 est responsable de l'accumulation intracellulaire des ions Cl- et de l'effet dépolarisant du GABA. Suite à une lésion, l'augmentation de la concentration intracellulaire en ions Cl- ([Cl-]i) permet une amélioration des capacités régénératives neuronales. Au cours de ma thèse, je me suis en premier lieu intéressé à la régulation de l'HC par interleukine 6 (IL6) en réponse à une lésion nerveuse. L'axotomie du nerf sciatique induit l'expression de l'IL6 et son récepteur IL6-Rα dans les neurones sensitifs des GRD lombaires L4-L5. Des mesures par patch perforé sur des neurones sensitifs en culture ont montré une augmentation de la [Cl-]i dépendante de l'IL6 dans une sous-population de neurones mécano- et proprioceptifs en réponse à l'axotomie. Cette régulation est permise par la phosphorylation à la membrane plasmique neuronale de NKCC1. Le co-transporteur KCC3 est impliqué dans une maladie génétique conduisant dès la naissance à une perte sensorimotrice, ce qui m'a conduit à étudier son rôle dans la régulation de l'HC des neurones sensitifs au cours du développement et chez l'adulte. Nos données ont démontré l'existence d'un « switch chlorure » développemental, diminuant la [Cl-]i. Ce switch est altéré chez la souris KCC3-/-, dans laquelle une partie des neurones a déjà diminué sa [Cl-]i. Au stade adulte, nous avons également observé un doublement de la [Cl-]i dans 30% des neurones sensitifs de souris KCC3-/-, pourcentage corrélé à la proportion de neurones WT exprimant KCC3. Ces données prouvent que KCC3 est impliqué, de manière directe ou non, dans la régulation de l'HC des neurones sensitifs au cours du développement et chez l'adulte. / Chloride homeostasis (CH) is a major component of nerve transmission. Interaction between the neurotransmitter GABA and his receptor, GABAA, allows chloride movements depending on electrochemical potential. In dorsal root ganglia (DRG) sensory neurons, the cation-chloride cotransporter NKCC1 is responsible for intracellular accumulation of chloride ions and depolarizing effects of GABA. After injury, an increase of intracellulaire chloride concentration ([Cl-]i) allows an improvement of neuronal regenerative capacities. In a first time, I worked on regulation of CH by interleukine 6 (IL6) in response to nerve injury. Axotomy of the sciatic nerve induces expression of IL6 and his receptor IL6-Rα in sensory neurons from lombar L4-L5 DRG. Perforated patch measurements of sensory neurons have demonstrated an increase of [Cl-]i depending on IL6 in a sub-population of mechano- and proprioceptors in response to lesion. This regulation is provided by phosphorylation at the neuronal plasma membrane of NKCC1. The cation-chloride cotransporter KCC3 is implicated in a hereditary syndrome leading after birth to sensorymotors defects. This is why I have studied his role in regulation of CH in sensory neurons during development and in adulthood. Data have shown the existence of a peripheral developmental “chloride switch”. This switch is abolished in KCC3-/- sensory neurons, in which a part of neurons has already decreased [Cl-]i. In adulthood, we also observed an [Cl-]i twice as much as WT in 30% of sensory neurons from KCC3-/- mice. This percentage is correlated to the proportion of WT neurons expressing KCC3. These results demonstrate for the first time that KCC3 is implicated in regulation of CH in sensory neurons during development and in adulthood.