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Murine small intestinal CD103+ dendritic cells (DCs) produce retinoic acid (RA) through retinaldehyde dehydrogenase (RALDH) activity, thereby inducing ‘gut-homing’ α4β7 and CCR9 on T cells they activate, enhancing TGF-β-mediated induction of Foxp3+ regulatory T cells and suppressing induction of pro-inflammatory TH17 cells. RALDH activity of CD103+ DCs is reduced in mouse models of inflammatory bowel disease (IBD) but the role of RALDH activity in human intestinal DCs in the pathogenesis of IBD is undefined. This project aimed to determine the influence of inflammation on RALDH activity of antigen presenting cell (APC) subsets including CD103+ DCs within human distal intestinal mucosa. RALDH activity was identified by Aldefluor assay in intestinal DCs (CD103+ and CD103- subsets) alongside ALDH1A2 expression in healthy controls. In contrast with mouse models, RALDH activity was not reduced in CD103+ DCs from IBD patients. An increased frequency of CD14+ macrophages (MФ) of IBD patients displayed ALDH1A1-associated RALDH activity compared with healthy controls. Blood CD14+ monocytes, putative precursors of intestinal CD14+ MФ, of healthy controls and IBD patients displayed ALDH1A1-associated RALDH activity indicating RALDH is systemically acquired by monocytes and upregulated within the mucosa of IBD patients, or alternatively that RALDH+ monocytes are selectively recruited in IBD. In vitro, inhibition of RA receptor-α signalling blocked GM-CSF-mediated differentiation of TNFα-producing pro-inflammatory RALDH+ CD14+ MФ from monocytes, consistent with enhanced RALDH activity of intestinal CD14+ MФ in IBD supporting a pro-inflammatory phenotype. Soluble intestinal mediators including prostaglandin E2 suppressed RALDH activity of MoDCs in vitro, whilst mediators from inflamed IBD mucosa conditioned MoDCs to imprint enhanced levels of α4β7 expression on naive CD4+ T cells independent of RALDH activity. This study provides the first systematic analysis of RALDH activity in human intestinal APCs and indicates important distinctions between mouse models and human IBD.

by Grant Richardson Stenton. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 259-287). / Abstract --- p.i / Acknowledgements --- p.iii / Publications --- p.iv / Abbreviations --- p.v / Contents --- p.vii / Chapter Chapter 1 --- Introduction / Chapter 1 1.1. --- Historical Background --- p.2 / Chapter 1.2. --- Origin and distribution of mast cells --- p.2 / Chapter 1.3. --- Mast cell heterogeneity --- p.3 / Chapter 1.4. --- Mast cell mediators --- p.5 / Chapter 1.4.1. --- Preformed mast cell mediators --- p.6 / Chapter 1.4.2. --- Newly synthesised mast cell mediators --- p.7 / Chapter 1.5. --- Mast cell activation --- p.11 / Chapter 1.5.1. --- Antigenic pathway of mast cell activation --- p.11 / Chapter 1.5.1.1. --- Antigen binding and receptor aggregation --- p.12 / Chapter 1.5.1.2. --- Early events following FcεRI aggregation --- p.13 / Chapter 1.5.1.3. --- Antigenic induction of mast cell second messenger production --- p.15 / Chapter 1.5.1.4. --- Phospholipase C activation and mast cells --- p.16 / Chapter 1.5.1.5. --- Phospholipase A2 activation and mast cells --- p.17 / Chapter 1.5.1.6. --- Intracellular calcium and mast cells --- p.18 / Chapter 1.5.1.7. --- Calcium and calmodulin --- p.21 / Chapter 1.5.1.8. --- Adenylate cyclase activation and mast cells --- p.21 / Chapter 1.5.2. --- Non-antigenic pathway of mast cell activation --- p.22 / Chapter 1.6. --- Aims of the study --- p.25 / Chapter 1.6.1. --- Diuretics --- p.26 / Chapter 1.6.2. --- Histamine receptor directed compounds --- p.27 / Chapter 1.6.3. --- Cyclo-oxygenase inhibitors --- p.28 / Chapter 1.6.4. --- Immunosuppressive compounds --- p.29 / Chapter Chapter 2 --- Materials and Methods --- p.31 / Chapter 2.1. --- Materials and methods --- p.32 / Chapter 2.1.1. --- Secretagogues --- p.32 / Chapter 2.1.2. --- Anti-allergic compounds --- p.32 / Chapter 2.1.3. --- Diuretics --- p.32 / Chapter 2.1.4. --- Immunosuppressants --- p.33 / Chapter 2.1.5. --- Histamine agonists and antagonists --- p.33 / Chapter 2.1.6. --- Cyclo-oxygenase inhibitors --- p.33 / Chapter 2.1.7. --- Materials for buffers --- p.34 / Chapter 2.1.8. --- Materials for rat sensitization --- p.34 / Chapter 2.1.9. --- Materials for histamine assay --- p.35 / Chapter 2.1.10. --- Materials for calcium measurement --- p.35 / Chapter 2.1.11. --- Materials for prostaglandin D2 measurement --- p.35 / Chapter 2.1.12. --- Materials for leukotriene C4 measurement --- p.36 / Chapter 2.1.13. --- Materials for cyclic AMP measurement --- p.36 / Chapter 2.1.14. --- Miscellaneous --- p.36 / Chapter 2.2. --- Buffers and stock solutions --- p.37 / Chapter 2.2.1. --- Buffer ingredients --- p.37 / Chapter 2.2.2. --- Stock solutions --- p.38 / Chapter 2.3. --- Animals and cell isolation --- p.39 / Chapter 2.3.1. --- Animals --- p.39 / Chapter 2.3.2. --- Sensitization of animals --- p.39 / Chapter 2.3.3. --- Cell isolation --- p.40 / Chapter 2.3.4. --- Cell washing and purification --- p.41 / Chapter 2.3.5. --- Preparation of cells for counting --- p.42 / Chapter 2.3.6. --- Cell counting on a haemocytometer --- p.42 / Chapter 2.4. --- General protocol for histamine release and histamine measurement --- p.43 / Chapter 2.4.1. --- Histamine release --- p.43 / Chapter 2.4.2. --- Spectroflurometric determination of histamine contents --- p.44 / Chapter 2.4.3. --- Calculation of histamine levels --- p.45 / Chapter 2.5. --- Protocol for cellular calcium measurement --- p.47 / Chapter 2.5.1. --- 45Ca2+ influx measurement --- p.47 / Chapter 2.5.2. --- Calculation of 45Ca2+ influx --- p.48 / Chapter 2.5.3. --- Fura-2 fluorescence measurement of intracellular calcium --- p.48 / Chapter 2.5.4. --- Fura-2 cell loading --- p.48 / Chapter 2.5.5. --- Fura-2 fluorescence parameters --- p.49 / Chapter 2.5.6. --- Calculation of basal calcium levels --- p.50 / Chapter 2.6. --- Protocol for prostaglandin D2 (PGD2) measurement --- p.52 / Chapter 2.6.1. --- PGD2 production --- p.52 / Chapter 2.6.2. --- Enzyme Immunosorbent Assay (EIA) method of PGD2 measurement --- p.52 / Chapter 2.6.3. --- Calculation of (EIA) PGD2 production --- p.53 / Chapter 2.6.4. --- Radio Immunosorbent Assay (RIA) method of PGD2 measurement --- p.53 / Chapter 2.6.5. --- Calculation of (RIA) PGD2 concentration --- p.54 / Chapter 2.7. --- Protocol for leukotriene C4 (LTC4) measurement --- p.54 / Chapter 2.7.1. --- LTC4 production --- p.54 / Chapter 2.7.2. --- Enzyme Immunosorbent Assay (EIA) method of LTC4 measurement --- p.55 / Chapter 2.7.3. --- Calculation of (EIA) LTC4 concentration --- p.55 / Chapter 2.8. --- Protocol for cyclic adenosine monophosphate (cAMP) measurement --- p.56 / Chapter 2.8.1. --- cAMP production --- p.56 / Chapter 2.8.2. --- Radio Immunosorbent Assay (RIA) method of cAMP measurement --- p.56 / Chapter 2.8.3. --- Calculation of cAMP concentration --- p.57 / Chapter 2.9. --- Statistical analysis --- p.57 / Chapter Chapter 3 --- "Frusemide, Bumetanide and DSCG" --- p.58 / Chapter 3.1. --- Introduction --- p.59 / Chapter 3.1.1. --- Frusemide and bumetanide as loop diuretics --- p.59 / Chapter 3.1.2. --- Effects of frusemide and bumetanide on the airways --- p.59 / Chapter 3.1.3. --- Effects of frusemide on mast cells --- p.60 / Chapter 3.1.4. --- Experimental aims --- p.61 / Chapter 3.2. --- Materials and methods --- p.62 / Chapter 3.3. --- Results --- p.63 / Chapter 3.3.1 --- "Effects of frusemide, bumetanide and DSCG on immunologically induced histamine release from rat peritoneal mast cells" --- p.63 / Chapter 3.3.2. --- "Effects of frusemide, bumetanide and DSCG on compound 48/80 induced histamine release from rat peritoneal mast cells" --- p.64 / Chapter 3.3.3. --- "Effects of frusemide, bumetanide and DSCG on compound 48/80 induced histamine release from rat peritoneal mast cells suspended in calcium free buffer" --- p.65 / Chapter 3.3.4. --- "Effects of frusemide, bumetanide and DSCG on ionophore A23187 and thapsigargin induced histamine release from rat peritoneal mast cells" --- p.65 / Chapter 3.3.5. --- Cross-tachyphylaxis effects of frusemide and bumetanide --- p.66 / Chapter 3.3.6. --- Effects of DSCG on the inhibition of anaphylactic histamine release due to frusemide --- p.67 / Chapter 3.3.7. --- Effects of frusemide and DSCG on immunologically and non-immunologically induced 45Ca2+ uptake --- p.67 / Chapter 3.3.8. --- Effects of frusemide and DSCG on immunologically and non-immunologically induced changes in the free intracellular calcium concentration of rat peritoneal mast cells --- p.68 / Chapter 3.3.9. --- Effects of frusemide and bumetanide on the spontaneous and secretagogue induced PGD2 production from rat peritoneal mast cells --- p.69 / Chapter 3.3.10. --- Effects of frusemide and DSCG on cellular cAMP levels --- p.70 / Chapter 3.4. --- Discussion --- p.101 / Chapter 3.5. --- Summary --- p.111 / Chapter 3.6. --- Conclusion --- p.114 / Chapter 3.7. --- Future studies --- p.114 / Chapter Chapter 4 --- Histamine Receptor Directed Compounds --- p.115 / Chapter 4.1. --- Introduction --- p.116 / Chapter 4.1.1. --- Histamine receptor subtypes --- p.116 / Chapter 4.1.2. --- Histamine effects on the airways --- p.117 / Chapter 4.2. --- Signal transduction mechanisms --- p.118 / Chapter 4.2.1. --- H1-receptors --- p.118 / Chapter 4.2.2. --- H2-receptors --- p.119 / Chapter 4.2.3. --- H3-receptors --- p.120 / Chapter 4.3. --- Histamine receptors and mast cells --- p.120 / Chapter 4.3.1. --- Effects of histamine agonists and antagonists on mast cells --- p.120 / Chapter 4.3.2. --- Experimental aims --- p.122 / Chapter 4.3.3. --- Materials and methods --- p.123 / Chapter 4.4. --- Results --- p.123 / Chapter 4.4.1. --- Effects of the test compounds on the spontaneous histamine release from rat peritoneal mast cells --- p.123 / Chapter 4.4.2. --- Effects of the test compounds on anti-IgE induced histamine release from rat peritoneal mast cells --- p.125 / Chapter 4.4.3. --- Effects of the test compounds on compound 48/80 induced histamine release from rat peritoneal mast cells --- p.126 / Chapter 4.4.4. --- Effects of the test compounds on anti-IgE and compound 48/80induced histamine release from rat peritoneal mast cells in calcium free buffer --- p.126 / Chapter 4.4.5. --- Effects of the test compounds on ionophore A23187 induced histamine release from rat peritoneal mast cells --- p.127 / Chapter 4.4.6. --- "Effects of histamine antagonists on dimaprit, imetit and impromidine induced histamine release from rat peritoneal mast cells" --- p.128 / Chapter 4.4.7. --- "Effects of anti-IgE, dimaprit and imetit on PGD2 production from rat peritoneal mast cells" --- p.128 / Chapter 4.4.8. --- "Effects of benzalkonium chloride (BAC) on dimaprit, imetit, compound 48/80 and anti-IgE induced histamine release from rat peritoneal mast cells" --- p.129 / Chapter 4.4.9. --- "Effects of pertussis toxin on dimaprit, imetit, compound 48/80and anti-IgE induced histamine release from rat peritoneal mast cells" --- p.129 / Chapter 4.4.10. --- "Effects of dimaprit, imetit, compound 48/80 and anti-IgE on the free intracellular calcium concentration of rat peritoneal mast cells" --- p.130 / Chapter 4.5. --- Discussion --- p.171 / Chapter 4.5.1. --- The possible existence of histamine receptors on rat peritoneal mast cells --- p.171 / Chapter 4.5.2. --- "Possible mechanism of action for the histamine releasing actions of dimaprit, imetit and impromidine on rat peritoneal mast cells" --- p.174 / Chapter 4.6. --- Conclusion --- p.181 / Chapter 4.7. --- Future studies --- p.182 / Chapter Chapter 5 --- Cyclo-oxygenase Inhibitors --- p.184 / Chapter 5.1. --- Introduction --- p.185 / Chapter 5.1.1. --- Cyclo-oxygenase isozymes --- p.185 / Chapter 5.1.2. --- Cyclo-oxygenase inhibitors and mast cells --- p.186 / Chapter 5.1.3. --- Experimental aims --- p.190 / Chapter 5.2. --- Materials and methods --- p.190 / Chapter 5.3. --- Results --- p.191 / Chapter 5.3.1. --- Effects of cyclo-oxygenase inhibitors on immunologically and non-immunologically induced histamine release from rat peritoneal mast cells - --- p.191 / Chapter 5.3.2. --- Effects of cyclo-oxygenase inhibitors on immunologically and non-immunologically induced PGD2 production from rat peritoneal mast cells --- p.192 / Chapter 5.3.3. --- Effects of cyclo-oxygenase inhibitors on immunologically and non-immunologically induced LTC4 production from rat peritoneal mast cells --- p.192 / Chapter 5.3.4. --- Effects of cyclo-oxygenase inhibitors on immunologically and non-immunologically induced 45Ca uptake by rat peritoneal mast cells --- p.193 / Chapter 5.4. --- Discussion --- p.221 / Chapter 5.5. --- Summary and Conclusion --- p.225 / Chapter Chapter 6 --- Immunosuppressive Drugs --- p.228 / Chapter 6.1. --- Introduction --- p.229 / Chapter 6.1.1. --- CsA and FK506 binding proteins --- p.230 / Chapter 6.1.2. --- Distribution of CyPA and FKBP12 --- p.231 / Chapter 6.1.3 --- Mechanism of immunosuppression --- p.232 / Chapter 6.1.4. --- The role of calcineurin in IL-2 promoter induction --- p.233 / Chapter 6.2. --- Immunosuppressive agents and mast cells --- p.234 / Chapter 6.2.1. --- Introduction --- p.234 / Chapter 6.2.2. --- CsA and FK506 inhibit mast cell cytokine production --- p.235 / Chapter 6.2.3. --- "CsA mediated inhibition of mediator release from, and calcium uptake by mast cells and basophils" --- p.236 / Chapter 6.2.4. --- Inhibition of mediator release from mast cells and basophils by FK506 --- p.239 / Chapter 6.2.5. --- Aim of this study --- p.240 / Chapter 6.2.6. --- Materials and methods --- p.241 / Chapter 6.3. --- Results --- p.241 / Chapter 6.3.1. --- Effects of CsA and FK506 on immunologically and non-immunologically induced histamine release from rat peritoneal mast cells --- p.241 / Chapter 6.3.2. --- Effects of CsA and FK506 on immunologically and non-immunologically induced PGD2 production from rat peritoneal mast cells --- p.242 / Chapter 6.3.3. --- Effects of CsA and FK506 on immunologically and non-immunologically induced 45Ca uptake by rat peritoneal mast cells --- p.243 / Chapter 6.4. --- Discussion --- p.254 / Chapter 6.4.1. --- "Effects of CsA on histamine release from, and 45Ca uptake by rat peritoneal mast cells, following immunological and non-immunological activation" --- p.254 / Chapter 6.4.2. --- Effects of CsA on PGD2 production from rat peritoneal mast cells --- p.256 / Chapter 6.4.3. --- "Effects of FK506 on histamine release from, and 45Ca uptake by rat peritoneal mast cells, following immunological and non-immunological activation" --- p.256 / Chapter 6.4.4. --- Effects of FK506 on immunological PGD2 production from rat peritoneal mast cells --- p.257 / Chapter 6.5. --- Summary --- p.257' / Chapter 6.6. --- Future work --- p.258 / References

Devant le succès maintenant bien démontré des prothèses totales de hanche, les chirurgiens sont amenés à proposer ce traitement chez des patients dont l’espérance de vie ne cesse d’augmenter. Parallèlement, une population plus jeune et active a aussi recours à ce traitement permettant de reprendre rapidement ses activités professionnelles et de loisirs. Des progrès exceptionnels ont été réalisés par les bio-ingénieurs en collaboration avec les chirurgiens dans la production industrielle d’implants en polyéthylène désormais très performants avec des taux d’usure très faibles. Néanmoins, bien que très diminuée, cette usure aboutit à la production de particules micrométriques libérées autour de la prothèse. Ces particules d’usure interagissent avec les tissus environnants et notamment les macrophages circulants, conduisant à une réaction inflammatoire. Les macrophages, cellules clés de cette cascade inflammatoire, subissent une activation par phagocytose ou par contact membranaire avec les particules puis une polarisation engendrant la libération de molécules à fort pouvoir inflammatoire : cytokines, chemokines, dérivés oxygénés, TNF-α et autres conduisant au maintien d’un niveau inflammatoire élevé autour de la prothèse. A long terme, le risque est l’évolution vers l’ostéolyse péri-prothétique et le descellement aseptique dont le seul traitement est la reprise chirurgicale, intervention difficile chez des patients qui ont vieilli. La compréhension des mécanismes biologiques de cette réaction inflammatoire permet le développement de stratégies modulant ou inversant cette inflammation afin d’augmenter la longévité des prothèses totales de hanche. / Total hip replacements are now very succesful and surgeons perform this procedure in patients with an increasing longevity. Young and active patients are also candidates for this surgery allowing them to quickly resume their professional and recreational activities. Exceptional advances have been made by bio-engineers and surgeons in the production of highly efficient polyethylene implants which have very low wear rates. Nevertheless, wear remains and wear particles are still released around the implant. These particles react with the surrounding tissues especially macrophages, leading to an inflammatory reaction. Macrophages are then activated and subsequently polarize releasing inflammatory factors such as cytokines, chemokines, oxide species and TNF-?. This could lead peri-prosthetic osteolysis and aseptic loosening requiring revision surgery, a difficult procedure. Understanding the biological mecanisms of this inflammatory reaction may help creating strategies to mitigate or reverse this inflammation with the goal to increase the longevity of these implants.

<p>Hos patient med inflammatory bowel diseases (IBD) har nutrition en central betydelse. Nutrition ska betraktas som en medicinsk behandling samtidigt som nutrition är ett av sjuksköterskans omvårdnadsansvar. Syftet var att belysa nutritionsbehovet hos patient med inflammatory bowel diseases. Resultatet baseras på 15 vetenskapliga artiklar. Resultatet visar att patient med IBD lider av malnutrition eller ligger i riskzon för att bli malnutrierad. Malabsorption är den viktigaste faktorn för malnutrition hos patient med Crohns sjukdom. Vid intag av hög andel fett i kosten minskar den terapeutiska effekten. Hos barn med Crohns sjukdom som lider av malabsorption och växthämning är polymerisk diet den främsta behandlingen. För patient med IBD är hälften elementaldiet och andra halvan valfri nutrition gynnsam då återfallsfrekvensen minskar. Lägre nivåer av mikropartiklar påvisas hos patient med IBD, där vitamin D brist ingår. Sjuksköterskans uppgift är att bedöma patients näringstillstånd genom ett komplett nutritionsstatus. Nutritionsstatus består av anamnes, kroppssammansättning, fysiska tecken, muskelstyrka och laboratorieprover. För att patient med IBD ska kunna använda sig av nutritionsbehandling krävs mer konkret vetenskaplig forskning om kostrekommendationer. Även utveckling av nuvarande standardvårdplaner som är otillräckliga behövs.</p>

Tous les êtres vivants présentent un arsenal de défenses contre les pathogènes, et la réponse inflammatoire constitue le processus initial de cette défense, qui s’achève par la réparation des tissus lésés. Paradoxalement, un processus inflammatoire prolongé est également associé à de nombreuses pathologies comme l’athérosclérose, l’asthme, les maladies auto-immunes mais aussi certains cancers. Le recrutement excessif de leucocytes au site de l’inflammation est un processus commun à ces pathologies. Dès lors, la compréhension et la maîtrise du phénomène complexe et finement orchestré de la migration sélective des populations leucocytaires, appelée chimiotactisme, sont des enjeux majeurs de la recherche médicale contemporaine. Les récepteurs aux peptides formylés bactériens et mitochondriaux (FPRs) forment la première famille de récepteurs chimiotactiques identifiée. Elle comprend trois membres, FPR1, 2 et 3, présentant un haut niveau de similitude et partageant certains de leurs multiples ligands. Le troisième membre de ce groupe, FPR3, reste actuellement le moins bien connu. Récemment, un agoniste de FPR3, affin et spécifique, a été identifié dans le laboratoire. Il s’agit du peptide F2L, qui correspond aux 21 premiers acides aminés de la protéine intracellulaire HEBP1. Dans le cadre de ce travail de thèse, nous nous sommes attelé à la caractérisation approfondie du récepteur FPR3 et son ligand peptidique F2L. Dans un premier temps, et à l’aide d’anticorps validés dans le cadre de ce travail, nous avons montré que le peptide F2L induit le chimiotactisme d’un ensemble de populations leucocytaires qui expriment FPR3, dont les sous-populations de macrophages des poumons, du colon et de la peau, les éosinophiles et les cellules dendritiques plasmacytoïdes. Cette distribution suggère, pour FPR3, une fonction dans la réponse inflammatoire. Nous avons pu montrer ensuite que F2L peut être généré par la protéolyse de son précurseur, HEBP1, sous l’action de la cathepsine D des macrophages. La cathepsine D est une aspartique protéase lysosomiale impliquée dans l’homéostasie cellulaire, les processus apoptotiques et inflammatoires physiologiques et pathologiques, et dans le développement tumoral. Il s’agit désormais d’identifier dans quel compartiment et sous quelles conditions F2L est produit et sécrété. Enfin, parallèlement à ces travaux, nous avons démontré que la cathepsine G, une sérine protéase contenue dans les granules azurophiles des neutrophiles, active également le récepteur FPR3. Des résultats préliminaires suggèrent un mode d’activation alternatif du récepteur, impliquant la protéolyse d’un troisième partenaire et la génération d’un agoniste actuellement non identifié. Le couple FPR3-F2L semble dès lors impliqué dans l’induction ou la résolution de la réponse inflammatoire en recrutant les éosinophiles, monocytes, macrophages et cellules dendritiques au site de la lésion.

The purpose of this study was to describe how adolescents aged 12-18 years with inflammatory bowel disease experience their illness and what coping strategies they use to manage their illness and improve their wellbeing. The method used was a descriptive literature study, and the result of the study included 15 scientific articles. Our results showed that IBD affected the adolescent’s everyday life and social life with friends, family and activities. The adolescents also reported that they experienced a feeling of vulnerability, altered body image and that they saw themselves as different from healthy subjects. Adolescents with IBD have been shown to use the same coping strategies that healthy adolescents are using, that is, confrontational, evasive, independent and optimistic coping. The avoidance coping is more prevalent in adolescents with IBD, as the use of such strategies is specific for IBD because of illness symptoms. There is a need for more research directed at young people with IBD, since previous research is based mostly on adults' experiences of illness.

Hos patient med inflammatory bowel diseases (IBD) har nutrition en central betydelse. Nutrition ska betraktas som en medicinsk behandling samtidigt som nutrition är ett av sjuksköterskans omvårdnadsansvar. Syftet var att belysa nutritionsbehovet hos patient med inflammatory bowel diseases. Resultatet baseras på 15 vetenskapliga artiklar. Resultatet visar att patient med IBD lider av malnutrition eller ligger i riskzon för att bli malnutrierad. Malabsorption är den viktigaste faktorn för malnutrition hos patient med Crohns sjukdom. Vid intag av hög andel fett i kosten minskar den terapeutiska effekten. Hos barn med Crohns sjukdom som lider av malabsorption och växthämning är polymerisk diet den främsta behandlingen. För patient med IBD är hälften elementaldiet och andra halvan valfri nutrition gynnsam då återfallsfrekvensen minskar. Lägre nivåer av mikropartiklar påvisas hos patient med IBD, där vitamin D brist ingår. Sjuksköterskans uppgift är att bedöma patients näringstillstånd genom ett komplett nutritionsstatus. Nutritionsstatus består av anamnes, kroppssammansättning, fysiska tecken, muskelstyrka och laboratorieprover. För att patient med IBD ska kunna använda sig av nutritionsbehandling krävs mer konkret vetenskaplig forskning om kostrekommendationer. Även utveckling av nuvarande standardvårdplaner som är otillräckliga behövs.

Pharmacokinetic parameters for theophylline and dyphylline were evaluated in horse cerebrospinal fluid (csf) and plasma. Pharmacokinetic parameters did not differ significantly (p > 0.05) at the same dose for either drug when administered alone or concomitantly. Theophylline and dyphylline penetrate horse csf to produce approximately 1/2 the concentrations found in plasma. Doubling the theophylline dose from 10 mg/Kg to 20 mg/Kg doubled both csf and plasma theophylline concentrations. However, doubling the dyphylline dose from 20 mg/Kg to 40 mg/Kg tripled both csf and plasma dyphylline concentrations. Simultaneous fitting between plasma and csf drug concentrations indicates that plasma is a good indicator for predicting csf concentrations for both theophylline and dyphylline. The influence of ibuprofen input rate on antipyresis was studied in rats with yeast induced fever. In addition, a data analysis comparison was made between rat data collected from this present study and literature data from fevered children. Counterclockwise hysteresis curves (ibuprofen plasma concentration versus temperature decrement) were observed following ibuprofen oral suspension when administered to rats and children. When the collapsed hysteresis curves were plotted (mean predicted total ibuprofen effect compartment concentration versus mean predicted temperature decrement effect) the rat and children's curves were not superimposable. However, the collapsed hysteresis curves of mean predicted ibuprofen unbound effect concentration versus mean predicted temperature decrement effect were superimposable for data from the rats and children. Based on mean unbound ibuprofen effect compartment concentration versus mean predicted temperature decrement effect, the antipyretic response to ibuprofen appears to be comparable between rats and children. The apparent qualitative trend in temperature decrement, although not statistically significant, perhaps due to variability, appears to be different among ibuprofen input regimens in rats. Maximum temperature decrement appears to relate not just to the concentration of ibuprofen obtained at steady-state, but the rate at which it is obtained. / Graduation date: 1993

The neuroprotective effects of AF4, a flavonoid-enriched extract derived from the peel of Northern Spy apples (containing quercetin-3-O-glucoside, quercetin-3-O-galactoside, quercetin-3-O-rhamnoside, quercetin-3-O-rutinoside, epicatechin, and cyanidin-3-O-galactoside) were examined by assessing neuronal loss and motor impairment resulting from hypoxic-ischemic (HI) brain injury in adult C57BL/6 mice. Relative to vehicle treatment (water, 10mL/kg/day), oral administration of AF4 (50 mg/kg/day) for 3 days reduces HI-induced neuronal loss in the striatum and hippocampus, motor impairments, and reduces the ability of LPS to stimulate the production of TNF-alpha in whole blood. Pretreatment with AF4 (1 ug/mL) decreased the death of mouse primary cortical neurons subjected to oxygen glucose deprivation (12 hours) in comparison to vehicle (DMSO) or the same concentration of quercetin or its metabolites. Taken together these findings indicate that AF4 reduces HI-induced brain injury and motor deficits by increasing the resistance of vulnerable neurons to ischemic cell death and decreasing the production of inflammatory cytokines.