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Tesis sobre el tema "Inflammation"
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1
Lawrence, Clifford M. "Anthralin inflammation". Thesis, University of Newcastle Upon Tyne, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390318.
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Warke, T. J. "Childhood airways inflammation". Thesis, Queen's University Belfast, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268984.
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Jatta, Ken. "Inflammation in Atherosclerosis". Doctoral thesis, Örebro : Universitetsbiblioteket, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-478.
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Gilroy, Derek William. "Cyclooxygenase 2 inflammation". Thesis, Queen Mary, University of London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265077.
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Limb, G. A. "Lymphokines in inflammation". Thesis, Brunel University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373086.
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Peters, Caren Lorraine. "Hypoxia in inflammation". Thesis, University of Bath, 2003. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426151.
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Sanchez, Moral Lidia. "Role of ZEB1 in adenoma formation, inflammation and inflammation-driven carcinoma". Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667993.
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Multiple studies have highlighted the role of ZEB1 as critical regulator of tumor progression through the regulation of different hallmarks of cancer beyond the induction of EMT. The general aim of this dissertation is to characterize new potential mechanisms that regulate oncogenic transformation in colorectal carcinoma. The specific objectives of this dissertation are:
1. To identify new roles and targets of the transcription factor ZEB1 as a mediator of Wnt-induced intestinal adenoma formation.
2. To characterize ZEB1’s mechanism of action as a transcriptional regulator in inflammation and inflammation-induced carcinomas.
To address these goals, a wide number of reagents and techniques have been used, namely, human samples of adenomas and CRC, CRC cell lines whose expression for different genes has been manipulated by overexpression or RNA interference, high throughput techniques (RNA and microbiota sequencing) and transgenic mouse models (ApcMin/+, Zeb1+/- and Mpg-/-).
We found that ZEB1 expression in epithelial cells from intestinal adenomas increases adenoma formation and decreases life span in the ApcMin/+ mouse model, which is supported by decreased senescence and apoptosis in ApcMin/+/Zeb1+/+ mice when compared to ApcMin/+/Zeb1+/- counterparts. ZEB1 is both a target and a mediator of the Wnt signaling pathway. Here we provide two new mechanisms by which ZEB1 modulates the Wnt pathway through the regulation of AXIN2 and DACT2 expression. In addition, we found that ZEB1 promotes lipid accumulation in adenomas and colorectal cancer cell lines through the repression of the ATGL/PPARα/PGC-1α axis, which is critical for the degradation of lipid droplets.
Besides, we show that ZEB1 is upregulated in the epithelial cells of ulcerative colitis patients and of mouse models of colitis, where its expression promotes intestinal inflammation and inflammatory tumorigenesis. ZEB1 exerts these functions, at least in part, through the increase of DNA damage and the inhibition of the MPG glycosylase, which is involved in DNA damage repair. Moreover, ZEB1 expression in CRC cells stimulates the production of ROS and IL1-β by macrophages which, in turn, reduce MPG expression in CRC cells.
Altogether, from the results presented in this dissertation, it can be concluded that:
1. ZEB1 represses senescence and apoptosis during Wnt-induced intestinal adenoma formation.
2. ZEB1 potentiates Wnt signaling in intestinal adenomas through the activation of AXIN2 and the repression of DACT2.
3. ZEB1 induces accumulation of lipids in intestinal cells through Wnt-dependent repression of ATGL, PPARα and PGC-1α.
4. ZEB1 is upregulated in the epithelial cells of UC patients and of mouse models of colitis, where its expression promotes intestinal inflammation and inflammation-driven tumorigenesis.
5. ZEB1 promotes colitis and inflammation-driven CRC through the induction of DNA damage and the inhibition of the DNA repair glycosylase MPG.
6. ZEB1 expression in epithelial cells stimulates the production of ROS and IL1-β by macrophages that, in turn, reduce MPG expression in CRC cells.
These results establish ZEB1 as an important regulator of intestinal adenoma formation, and describe ZEB1 as a mediator of inflammation and inflammation-driven carcinogenesis, setting ZEB1 as a potential therapeutic target in colorectal carcinoma.Múltiples estudis han destacat el paper de ZEB1 com a regulador essencial de la progressió tumoral a través de la regulació de varis dels trets distintius del càncer més enllà de la inducció de la transició epiteli-mesènquima (EMT). Els resultats presentats en aquesta tesi indiquen que ZEB1 regula la formació de tumors intestinals des de les fases més inicials, i descriuen ZEB1 com un important inductor de colitis i de càncer de colon induït per inflamació. Hem trobat que l’expressió de ZEB1 en cèl·lules epitelials d’adenomes intestinals augmenta la formació d’adenomes i redueix la supervivència en el model de ratolí ApcMin/+. A més, en comparació amb els ratolins ApcMin/+/Zeb1+/+, els ratolins ApcMin/+/Zeb1+/- presenten més senescència i apoptosi. ZEB1 és tant una diana com un mediador de la via de senyalització Wnt. Els nostres resultats proporcionen dos nous mecanismes pels quals ZEB1 interacciona amb la via Wnt a través de la regulació de l’expressió d’AXIN2 i DACT2. Addicionalment, hem observat que ZEB1 promou l’acumulació de lípids a través de la repressió de l’eix ATGL/PPARα/PGC-1α, el qual té un paper crític en la degradació de les vesícules lipídiques. En paral·lel, hem demostrat que ZEB1 es troba sobreexpressat en cèl·lules epitelials de pacients de colitis ulcerativa i en models murins de colitis, on la seva expressió promou la inflamació intestinal i la tumorogènesi derivada de la inflamació. ZEB1 exerceix aquestes funcions, al menys en part, a través de l’augment de les lesions en l’ADN i la inhibició de MPG, una glicosilasa implicada en la reparació de les lesions en l’ADN. A més, l’expressió de ZEB1 en les cèl·lules de càncer de colon estimula la producció d’espècies reactives d’oxigen (ROS) i IL-1β per part dels macròfags que, a la vegada, redueix els nivells de MPG en les cèl·lules de càncer de colon. En conjunt, aquests resultats estableixen ZEB1 com un element regulador de la formació d’adenomes intestinals, així com un mediador de la inflamació i la carcinogènesi derivada de la inflamació, confirmant ZEB1 com a potencial diana terapèutica en càncer colorectal.
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Levick, Scott P. "Inflammation and cardiovascular remodelling /". [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19090.pdf.
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Blomgran, Parmis. "Inflammation and tendon healing". Doctoral thesis, Linköpings universitet, Avdelningen för Kirurgi, Ortopedi och Onkologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-142349.
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Tendons heal through three different overlapping phases; the inflammatory, proliferative and remodeling phase. Many studies have investigated what factors influence healing of tendons. However, little was known about inflammation and the immune cells present during Achilles tendon healing by the time this thesis started. We developed a flow cytometry method for our rat model of tendon healing, which enabled us to study different leukocyte subpopulations during Achilles tendon healing. The general aim of this thesis was to understand more about inflammation and the immune cell populations present during tendon healing and how the immune cell composition changes during normal tendon healing. Moreover, we investigated how different factors that are known to influence tendon healing affected the composition of the immune cell population. First, we described the immune cells during the time course of tendon healing focusing on different subpopulations of macrophages and T cells. Then, we studied how these cells were influenced by reduced mechanical loading. Mechanical loading prolonged the presence of M1 macrophages and delayed the switch to regulatory T cells and M2 macrophages compared to reduced mechanical loading. Next, the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the leukocyte composition revealed that, even though NSAIDs influence the mechanical properties of healing tendon, this effect was not mediated via changes in the leukocyte sub-populations during early and mid-time tendon healing. Further, the effect of corticosteroids during the inflammatory and remodeling phases of tendon healing was an improved healing of tendons and a reduction of CD8a T cells when corticosteroid was administered after the inflammatory phase. Lastly, we investigated if impairment of tendon healing by NSAIDs was related to mechanotransduction or microdamage during mechanical loading and showed that NSAIDs impair tendon healing by reducing the response to microdamage. In conclusion, these studies show that inflammation plays an important role during Achilles tendon healing, and factors that influence healing can also alter the presence or polarization of immune cell populations.
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Eustace, Andrew David. "Syndecan 3 and inflammation". Thesis, University of Bristol, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.720843.
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Kamath, S. V. "Inflammation in paediatric asthma". Thesis, Queen's University Belfast, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269034.
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Mihaylova, Dessislava Dimitrova. "Submicron Particles and Inflammation". Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for bioteknologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-18590.
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Iron nanoparticles occur naturally in the environment, but their exposure increases dramatically due to the field of nanotechnology and –medicine. It is poorly understood how the intracellular cooperative mechanisms of submicron particles and microorganisms function on mammalian immune system. In this study, superparamagnetic iron oxide (SPIO) submicron particles will be used to benefit the research within environmental diseases, addressing the biocompatibility of these particles. The size-dependent effects in the immune system of two carboxyl coated SPIO particles with stated sizes 100 nm and 1 µm will be studied in vitro. It would be interesting to determine whether these particles were able to activate the inflammasome, but still, the precise molecular mechanisms for the activation remain unknown. In order to reveal the biocompatibility of these particles, tests were performed as a function of particle concentration ranging from 0.01 to 100 µg/mL using both whole blood and peripheral blood mononuclear cells (PBMC) isolated from healthy donors. The monocytes were first primed with Lipopolysaccharide from Escherichia coli 0111:B4 strain, followed by stimulation with increasing concentrations of the submicron particles. Flow cytometry on whole blood samples identified up-regulation of CD11b monocytes and granulocytes by the particles. In addition, Terminal Complement Complex analyses proved activation of the complement system. It is possible that the particles have been coated with C3b by the complement and phagocytized by the monocytes through CD11b/CD18 receptor. Cytokine secretion from monocytes and whole blood was measured with sandwich ELISA and Bio-plex. The smaller particles seemed to induce higher inflammatory responses than the larger ones. It was, however, interesting to find that the particles themselves caused secretion of active IL-1β without being primed in advance. The mechanisms of the NLRP3 inflammasome activation might be explained by ROS production due to iron imbalance in the cytoplasm. Toxicity of the particles was seen at 10 µg/mL, suggesting their potentially low biocompatibility above this concentration. However, it is suggested better biocompatibility of the silica coated 1 µm particles than the polysaccharide coated 100 nm particles.
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Higgins, Lisa Mary. "Regulation of intestinal inflammation". Thesis, Queen Mary, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322813.
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Farrell, Adrian J. "Mediators of synovial inflammation". Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284326.
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Kaplan, Jennifer Melissa. "Immunomodulation During Systemic Inflammation". University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1186158205.
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Scotte, Michel. "Régénération hépatique et inflammation". Rouen, 1997. http://www.theses.fr/1997ROUES042.
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Une des plus étonnantes propriétés du foie est sa capacité à réguler sa croissance et sa taille. Ce phénomène de régénération hépatique (RH) est sous l'influence de facteurs de croissance qui agissent sur le foie de manière autocrine, paracrine ou endocrine. La réponse inflammatoire (RI), réponse homéostatique de l'organisme à différentes agressions, est sous la dépendance de cytokines qui induisent les modifications hépatiques de la synthèse protéique. Des interactions fortes existent entre ces deux phénomènes puisque l'hépatectomie induit une RI et que la RI semble avoir une influence sur la RH. Le but de notre travail a donc été d'analyser l'expression de ces différents facteurs au cours de la RH et de trouver un modèle expérimental qui, en associant les deux phénomènes, permettrait d'obtenir une amplification de la RH. Nos résultats nous ont permis de montrer : - que la RH survient quelle que soit l'importance de la resection - que l'hépatectomie induit une RI dont la cinétique et l'amplitude varient en fonction de l'importance de la resection hépatique, - que cette RI s'exprime majoritairement par une synthèse systémique de cytokines qui agissent sur le foie par voie endocrine. - qu'une production intra-hépatique de cytokines peut survenir dans un modèle de rats endotoxémiques et agir par un mécanisme paracrine pour entraîner les modifications de synthèse protéique hépatique, - enfin, que l'existence d'une RI préalable à une hépatectomie entraîne une synthèse autocrine d'HGF par l'hépatocyte et une accélération de la RH. Ces résultats nous amènent à conclure que l'inflammation pourrait avoir une influence majeure sur la RH. Une meilleure connaissance des mécanismes de régulation concernant le priming des hépatocytes, l'expression des facteurs de croissance, de leurs récepteurs et les interactions entre les différentes populations cellulaires du foie permettrait une application clinique dans tous les domaines où ce phénomène de RH est impliqué.
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Meng, Luxi. "Adipocytes, Macrophages and Inflammation". Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/10183.
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While there is a very strong correlation between obesity and the development of insulin resistance and Type II diabetes, the molecular mechanisms involved are still unknown. However, one clue is that in both human subjects and animal models, obese adipose tissue is infiltrated with M1 macrophages and this creates a systemic low-grade, chronic inflammatory state that could be responsible for the negative consequences of obesity. A better understanding of the relationship between the adipocytes and macrophages under the inflammatory milieu may inform intervention strategies. In this study, the cross-talk between adipocytes and macrophages were investigated under inflammation at a transcriptional level. The gene expression of the adipocyte, 3T3-L1, was monitored in response to the pro-inflammatory secretions from an activated macrophage, RAW 264.7 cells. It was found that following exposure to this pro-inflammatory cocktail, adipocytes were able to respond to inflammatory stimuli in much the same way as immune cells, and displayed transient and drastic transcriptional regulation. Most excitingly, we showed that adipocytes exhibit a transcriptional memory effect, with the expression of many being quite different upon rechallenge with a second stimulus when compared to naïve cells. Microarray analysis revealed that this “memory” was demonstrated in a diverse group of sequences that were both up and down-regulated, including inflammatory and adipocyte-specific function associated sequences. Results suggested that the mechanism(s) behind this memory effect were both transcriptionally and post-transcriptionally regulated. Overall, this thesis shows that the inter-cellular communication between adipocytes and macrophages is strongly dependent on the environmental and temporal context of the adipocytes. This has far reaching implications for the study of the aetiology of the inflammatory state in obesity and, ultimately, the relationship between overweight and disease.
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Sobowale, Oluwaseun. "Intracerebral haemorrhage and inflammation". Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/intracerebral-haemorrhage-and-inflammation(7139560f-bd3c-4ff0-b628-f86ffc6477d2).html.
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Intracerebral haemorrhage (ICH) is a significant healthcare concern worldwide. Following ICH, primary injury occurs due to physical injury to neurones and glia as a result of mass effect from the haematoma. Secondary mechanisms of injury include haematoma expansion, toxic effects of the products of coagulation and blood breakdown products and sterile inflammation. Perihaematomal oedema can exacerbate mass effect in the acute and sub-acute phase of ICH. At present, the pathophysiology behind the secondary mechanisms of injury following ICH is not fully understood and this has led to inability to translate new treatments from bench to bedside. Haematoma expansion is a significant contributor to neurological deterioration in the acute phase; however, understanding of the factors leading to a third of patients developing haematoma expansion is limited. This thesis presents the results of work aiming to develop a reproducible model of haematoma expansion in preclinical ICH. Using this model we found that a systemic inflammatory stimulus failed to induce haematoma expansion in spontaneously hypertensive rats or their healthy controls. We gained further insight into factors that may contribute to haematoma expansion in ICH by studying the proteomic profile of patients in clinical ICH. We demonstrate the feasibility of multi-modality brain imaging in sub-acute ICH, which we propose will be a useful tool to monitor neuro-inflammation in the acute stages if the disease. Finally, we investigated the association between peripheral markers of inflammation (white blood cell count and C-reactive protein) and perihaematomal oedema at baseline and clinical outcome (mortality at 30 days). Our findings suggest that acute inflammation may drive acute perihaematomal oedema and interestingly, we found a negative association between C-reactive protein at baseline and 30-day mortality. Our findings are significant in the field of clinical ICH, and suggest that the inflammatory response is important. We will take our findings forward in future work with the goal of understanding why haematoma expansion occurs, with the aim of developing a test to identify patients at highest risk and interventions to improve outcome after ICH.
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Zanoli, Luca Maria. "Inflammation and arterial stiffness". Doctoral thesis, Università di Catania, 2012. http://hdl.handle.net/10761/1088.
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Arterial stiffness is one of the earliest detectable manifestations of adverse structural and functional changes within the vessel wall. It is well known that increased large artery stiffness independently predicts the cardiovascular risk in a variety of populations. The identification of populations at higher risk of increased arterial stiffness and the knowledge of the mechanisms involved in arterial stiffening may help to identificate pharmacological and other treatments to reduce the arterial stiffness and improve the outcome of the patients. Recently, new advances have been proposed about the active role of inflammation and endothelial dysfunction in arterial stiffening and early atherosclerosis. The aims of this thesis were to review the literature and to study, for the first time, the arterial stiffness in inflammatory bowel disease.
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Mäki-Petäjä, Kaisa Maria. "Inflammation, arterial stiffness and endothelial dysfunction : rheumatoid arthritis, a model of systemic inflammation". Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612095.
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Zhao, J. "The roles of myeloid derived cells in retinal inflammation and inflammation-mediated retinal angiogenesis". Thesis, Queen's University Belfast, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677966.
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Intraocular inflammation encompasses a diverse group of diseases which account for up to 20% of severe vision loss, particularly following pathological neovascularisation in the retina. Nowadays, the use of corticosteroids is still the main armamentarium to manage these devastating conditions. Clearly safer, more target-specific and effective drugs are needed. Experimental autoimmune uveoretinitis (EAU) is an animal model for human intraocular inflammation. It is well known that myeloid derived cells substantially contribute to the pathological activities in this model. The aims of my PhD project were: to understand how myeloid-derived cells contribute to retinal damage in the EAU and to investigate whether modulating these cells can control retinal inflammation and associated retinal angiogenesis. Firstly, we showed that the deletions of both CCL2 and CX3CR1 resulted in reduced retinal inflammation in EAU. In the CCL2/CX3CR1 double knockout EAU mice, the macrophage infiltration was reduced and the inflammation was dominated by neutrophils at the acute stage. A reduction in macrophage infiltration was associated with reduced retinal angiogenesis at the chronic stage of EAU. Secondly, we found that SOCS3 in myeloid cells played an important role in EAU. The LysM-Cre-SOCS3f11f1 mice had an earlier onset and more severe retinal inflammation after immunisation. LysM-Cre-SOCS3f11f1 EAU mice also developed more severe retinal angiogenesis. Inflammation in the LysM-Cre-SOCS3f11f1 EAU mice was characterised by enhanced neutrophil infiltration and greatly increased cytokine expressions. In addition, the bone marrow-derived macrophages from LysM-Cre-SOCS3f11fl mice expressed M2 makers and produced more IL-10 and VEGF-A compared to the cells from wr mice. Finally, we found that blocking CCL2 or VEGF-A alone was not sufficient to suppress chronic inflammation-mediated retinal angiogenesis. However, systemic inhibition of arginase-1 activity was effective in reducing chronic EAU induced retinal angiogenesis. Thus, arginase inhibition could be a novel therapeutic strategy to control retinal neovascularisation related to long-standing uveoretinitis.
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Chapman, Katie. "Peripheral inflammation after experimental stroke". Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.518434.
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Downey, D. G. "Airways inflammation in cystic fibrosis". Thesis, Queen's University Belfast, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269047.
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Liu, Jia Clinical School Prince of Wales Hospital Faculty of Medicine UNSW. "Nitric oxide in airway inflammation". Publisher:University of New South Wales. Clinical School - Prince of Wales Hospital, 2009. http://handle.unsw.edu.au/1959.4/43678.
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Exhaled breath condensate (EBC) is a non-invasive method of investigating airway inflammation associated with nitric oxide (NO) and the metabolites nitrite/nitrates (NOx) in diseases such as chronic obstructive pulmonary disease (COPD), but some of the variables affecting the results are unknown. It was hypothesised that 1) EBC would be influenced by lung volumes and the type of EBC collection device; 2) fractional exhaled NO (FENO) and EBC NOx in COPD patients would be altered by smoking and glucocorticosteroids (GCS); 3) cigarette smoke could contribute to the EBC NOx concentration while it may also decrease FENO indirectly by converting airway NO to NOx. It was found that EBC volume was significantly correlated with both tidal volume and minute volume. Comparing four EBC collection devices demonstrated greater efficiency with the ECoScreen?? than siliconised glass tubes or RTube?? but it gave factitiously high NOx levels. Total EBC protein levels over a 10-minute collection were significantly higher using the ECoScreen?? than either glass or RTube?? devices. A cross-sectional study of 96 COPD patients and 80 age-matched control subjects demonstrated that FENO levels in COPD patients were significantly higher than normal subjects when comparing either the combined groups or appropriate two subgroups: ex-smokers and smokers. GCS treatment demonstrated no significant effect on either FENO levels or EBC NOx, but EBC NOx was elevated in smokers. In vitro, cigarette smoke extract (CSE) induced significantly higher NOx and asymmetric dimethylarginine (ADMA) levels in A549 cells when compared with control media. The anti-oxidant, NAC pre-treatment partially reversed the elevated NOx levels but not the ADMA levels. This thesis is the first to report FENO and EBC NOx in COPD patients in an appropriate sample size to be able to evaluate each subgroup, and the increased EBC NOx levels found in smokers in vivo was consistent with the elevated NOx level in response to CSE observed in vitro. These data indicate that smoking-related airway inflammation and activation of the NO pathway are complex with both an increase in ADMA, NO, NOx and may be regulated by oxidative stress rather than the nitric oxide synthase (NOS) pathway.
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Bathoorn, Derk. "COPD exacerbations, inflammation and treatment". [S.l. : Groningen : s.n. ; University Library of Groningen] [Host], 2007. http://irs.ub.rug.nl/ppn/304982296.
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Parums, D. V. "Studies on inflammation in atherosclerosis". Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235059.
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A spectrum of chronic inflammation is commonly seen in association with advanced human atherosclerosis. This local complication of advanced atherosclerosis is termed 'chronic periaortitis'. This may be seen sub-clinically in necropsy samples or may present clinically, in more severe cases, as the conditions previously termed 'idiopathic retroperitoneal fibrosis', 'inflammatory aneurysm' or 'peri-aneurysmal retroperitoneal fibrosis'. The inflammatory cells consist of lymphocytes and plasma cells. Thinning or breaching of the media is common to all forms. A histological survey of necropsy material and surgical material has confirmed the unifying concept of chronic periaortitis. Histochemical, immunohistochemical, immunofluorescence and electron microscopy have been used in this study to examine the nature of the inflammatory response. Locally activated B lymphocytes are stimulated to produce immunoglobulin, predominantly IgG, to oxidised low density lipoprotein (LDL) and ceroid elaborated with human atheroma. T helper lymphocytes and HLA-DR positive cells mediate this response. These findings have been confirmed using in vitro culture of lymphocytes derived from tissue and peripheral blood of patients with chronic periaortitis. Antibodies to oxidized LDL and ceroid have been detected in serum from patients with chronic periaortitis using a modified ELISA technique. This has led to the development of a potential diagnostic test for chronic periaortitis. These results support the hypothesis that chronic periaortitis has an auto-allergic cause and that the allergen is a component of ceroid, likely to be oxidized LDL, elaborated in human atherosclerotic plaques.
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Warland, David Anthony. "Inflammation, the microcirculation and microalbuminuria". Thesis, Northumbria University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416355.
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Iannitti, Tommaso. "Obesity, inflammation and pathological pain". Thesis, Glasgow Caledonian University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555680.
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Obesity has become a concern of epidemic proportion and is associated with an increased incidence in chronic pain but the underlying mechanism is not known. Obesity is associated with a low-grade inflammation of white adipose tissue due to a dysregulation in cytokines and adipokines, some of which, including turnor necrosis factor-α and interleukin-1β, have been linked to inflammatory pain. Other adipokines such as adiponectin, display anti- inflammatory properties but their role in modulating inflammatory pain has not been investigated. The aim of this project was to characterise inflammatory pain in the Zucker fatty rat (fa/fa) model of obesity and identify a role for adipokines in mediating this process. It is hypothesised that adipokines, particularly adiponectin, which is lowered on the onset of obesity and possesses anti-inflammatory properties, may account for the differences in pain occurring with obesity. Body weights, blood glucose, plasma lipoproteins and serum triacylglycerol, cholesterol, phospholipids and insulin were measured in adult male lean and obese Zucker rats. Hindpaw withdrawal latency (secs) to thermal stimulation and response threshold (grams) to mechanical stimulation were measured before and after intraplantar injection of carrageenan, capsaicin or hindpaw-incision, and treatment with morphine in lean and obese rats. The effects of recombinant adiponectin or drug-vehicle administered intrathecally or intraplantarly on carrageenan-induced pain and inflammation were also measured in adult male Wistar rats. Expression of adiponectin, adiponectin receptor 1, adiponectin receptor 2, resistin, tumor necrosis factor-a, interleukin-Iβ mRNA in spinal cord, brain and adipose tissues and blood was compared in lean and obese rats and in response to intraplantar injection of carrageenan/saline, using polymerase chain reaction methodologies. Obese Zucker rats had increased body weight, serum cholesterol, phospholipid and insulin levels compared to lean rats. No differences in serum triglyceride levels were observed. Following carrageenan-induced inflammation, obese rats were more sensitive to mechanical and thermal stimulation of the inflamed paw, and displayed greater paw oedema compared to lean rats. No difference in capsaicin- or paw-incision induced-mechanical and thermal hyperalgesia or in morphine-induced analgesia was observed. Adiponectin, resistin, adiponectin receptor 1 and adiponectin receptor 2, tumor necrosis factor-a and interleukin-l P mRNA were all found to be constitutively expressed in spinal cord, brain, adipose tissue and blood. In obese rats adiponectin mRNA was down-regulated in spinal cord compared to lean rats, while an increase was observed in brain tissue. A decrease in adiponectin was also observed in paw tissue from carrageenan-treated Wistar rats compared to saline-treated rats. Intrathecal but not intraplantar injection of recombinant adiponectin inhibited mechanical allodynia and carrageenan-induced peripheral inflammation of the paw. The present study confmns that the Zucker fatty rat is a reliable model of obesity with well defined metabolic characteristics. The increase pain sensitivity and inflammatory response in these rats supports the evidence that obesity is a chronic low-grade inflammatory disorder where further inflammatory challenge leads to an augmented inflammatory and nociceptive response. The results strongly suggest that alterations in adipokine-mediated signalling, in particular involving adiponectin, may account for changes in inflammatory pain occurring with obesity making it a valuable target for pain management in these individuals.
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Stevenson, Diane J. "P2X7, inflammation and gastrointestinal disease". Thesis, University of Nottingham, 2008. http://eprints.nottingham.ac.uk/28897/.
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The inflammatory bowel diseases, ulcerative colitis and Crohn's disease are characterised by spontaneously relapsing and remitting inflammation, associated with increased mucosal levels of the inflammatory cytokine, interleukin-1 (IL-1)β. IL-1β processing and release is mediated by ATP stimulation of the purine receptor, P2X7. P2X7 is a membrane ion channel highly expressed in immune cells. Signal transduction occurs via rapid cation exchange, plasma membrane depolarisation and increased intracellular calcium. Additionally, prolonged or repeated P2X7 stimulation leads to formation of a non-selective membrane pore permeable to small molecules, and ultimately to cell death. The aim of this project was to investigate the properties of the P2X7 receptor in mononuclear cells, to show that it is associated with IL-1β release in the colon, and that this release can be modified by P2X7 antagonists. Studies of ethidium bromide uptake, a functional assay, showed that P2X7 receptors are present on LPMCs and displayed properties similar to those of PBMCs and THP-1 cells. P2X7 receptor-stimulation released mature IL-1β from LPMCs in a dose-dependent manner that, in IBD patients, matched the severity of their inflammation, and could be markedly reduced by P2X7 antagonists. P2X7 stimulation also results in increased exposure of phosphatidylserine on the outer cell membrane (PS flip), often considered to be a marker of apoptotic cell death. P2X7-stimulated PS flip however is reversible and is not associated with cell death following brief stimulation times. Cell death caused by longer stimulation did not have features of apoptosis, was more evident in monocytes than lymphocytes, with LPMCs being less susceptible than PBMCs and THP-1 cells. These studies have shown that the P2X7 receptor is intimately involved in the release of IL-1β from human colonic mononuclear cells, that the release is greater in cells from IBD tissue and can be markedly inhibited by P2X7 antagonists.
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Marsden, Paul Anthony. "Cough, asthma and airways inflammation". Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516825.
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Rationale Cough is an important symptom in asthma. In addition, cough is both troublesome to patients and may be important in the development of more severe disease. Moreover, it is a key symptom in the diagnosis of asthma, according to international guidelines. Little is known regarding the mechanism of cough in asthma. Until now, subjective measures of cough have been used in mechanistic and therapeutic studies relating to both cough in asthma and chronic cough. There is no published literature documenting cough rates in asthma or the relationship between cough rates and both subjective measures of cough and asthma control. In addition, the relationship between objective cough rates and airway inflammation, and the effects of cough on airway function and inflammation is unknown. Methods A series of studies was designed and carried out to answer the above questions. Firstly, a cross sectional study examining the relationships between objective and subjective measures of cough in classical asthma (CA), secondly a longitudinal study examining the relationship between cough rates and CA control and thirdly a cross-sectional study examining the effects of voluntary cough on airway function and inflammation. Results There was a poor correlation between objective and subjective measures of cough in CA. Cough-related quality of life correlated most closely with cough rates. Traditional measures of CA (e.g. spirometry) poorly reflected cough rates. Objective cough rates and sputum eosinophils were predictive of CA control as defined by ACO. Objective cough rates did not reflect sputum inflammatory cell count or mediators. Voluntary cough induced small changes in peak flow in mildmoderate CA and small changes in sputum ECP that were not reflected by changes in sputum eosinophils. Conclusions Subjective measures of cough in asthma are poor substitutes for objective cough rates. When designing studies for cough in asthma, both objective cough rates and cough-related quality of life should be incorporated. Objective cough rates reflect asthma control (independent of airway inflammation) more closely than traditional measures of asthma. Airway inflammation does not appear to directly reflect cough rates. In addition, short bouts of coughing in mildmoderate asthma induce neither significant changes in airway function nor airway inflammation.
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Daugherty, Alan. "Lipoproteins, inflammation, and vascular disease". Thesis, University of Bath, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425851.
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The major focus of the studies described in this thesis is the interaction of lipoproteins and inflammation in vascular diseases. Early studies describe the role of postprandial lipoproteins in the development of lipid-laden macro phages that are a hallmark of atherosclerotic lesions. These studies paved the way for subsequent studies on the role of lipoprotein modification in atherosclerosis. These included the discovery that LDL present in atherosclerotic lesions had properties that were consistent with oxidative modification. To determine whether this modification was a cause or consequence of the disease, studies were performed using antioxidants. These studies defined the effects of antioxidants on early and mature atherosclerotic lesions, as well as on iatrogenic vascular lesions. My laboratory also studied two potential enzymes that have the potential to generate oxidized lipoprotein; myeloperoxidase and 15-lipoxygenase. The effects of pharmacological inhibition and regulation on the latter enzyme were defined. Studies have also addressed the regulation and function of a major receptor for oxidized LDL, class A scavenger receptor. These include regulation, structure-function, and the effects of cell selective overexpression. These lipoprotein modifications have a well characterized role on the infiltration of macro phages and their subsequent engorgement with lipid. Aberrant lipoprotein metabolism may be a factor underlying the recruitment of T Iymphocytes into lesions. Generally, T Iymphocytes have an under appreciated role in the atherogenic process. Studies using mice deficient in Iymphocyte subclasses and specific cytokines are addressing the issue of this cell type in lesion formation. Finally, we have recently discovered a pronounced inflammatory role of angiotensin II that is associated with the development of atherosclerosis and abdominal aortic aneurysms
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Poxon, Valerie Anne. "Gastrointestinal inflammation and mucus biosynthesis". Thesis, Birmingham City University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334499.
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Wilson, Susan Jane. "Mucosal inflammation in allergic rhinitis". Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295233.
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McNulty, Clare. "Ageing, inflammation and cardiovascular function". Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6541/.
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Age is associated with the development of multi-system function loss including the musculoskeletal, immune and cardiovascular system, as well as body composition changes. These age-related alterations lead to frailty development and disease progression, reducing quality of life. A major lifestyle change occurring in later years is reduced physical activity levels. This thesis sought to examine the associations between physical activity and multi-system function loss in a cohort of elderly individuals, and to better understand the neural mechanisms underpinning the circulatory responses to exercise. It was observed that high daily physical activity levels attenuate some but not all of the age-related changes in elderly individuals. High physical activity was associated with superior physical functioning, lower total body fat and visceral adiposity, and plasma plasminogen activator inhibitor 1 (PAI-1) concentrations. Left ventricular (LV) diastolic function was negatively associated with mean arterial pressure (MAP) and visceral adiposity, suggesting that elderly individuals with higher MAP and visceral adiposity may have inferior LV diastolic function. In terms of neural mechanisms related to circulatory responses to exercise, in models of metaboreflex over-activity whereby BP is elevated as observed in heart failure patients, left atrial systolic function is enhanced in order to maintain end-diastolic volume and SV.
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De, Pablo Paola. "The epidemiology of musculoskeletal inflammation". Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4161/.
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Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction often resulting in functional disability and increased mortality. With appropriate therapies, it is possible to delay or even prevent evolution of patients into RA and/or induce remission. Thus the identification of individuals not only early in the disease course but at risk of developing RA is important. Following on this concept, we investigated the presence of systemic autoimmunity among individuals at risk of RA based on environmental exposures, and conducted a meta-analyses showing an early therapeutic window of opportunity associated with sustained benefit on disease progression and structural damage. Since time matters, we examined both the recent criteria performance and the role of musculoskeletal ultrasound as tools to identify RA early in the disease course. One of the therapeutic goals in RA is the prevention of radiologically evident joint destruction, thus we evaluated a novel scoring method to assess radiological disease progression. We also examined the impact of inflammation on RA-associated collateral damage, including cardiovascular disease and bone loss. We observed within the epidemiology of musculoskeletal involvement that chronic inflammation in any one tissue clearly impacts the overall health status and disease susceptibility of the whole body.
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Brügel, Mathias [Verfasser]. "Biomarker der Inflammation / Mathias Brügel". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2021. http://d-nb.info/1227840144/34.
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Holm, Angelika. "Aquaporins in Infection and Inflammation". Doctoral thesis, Linköpings universitet, Avdelningen för mikrobiologi och molekylär medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-127500.
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The ability of eukaryotic cells to change their shape and to migrate directionally is highly dependent on active volume regulation in cells building up tissues as well as in individual cells. Transmembrane fluxes of water via specialized water channels, called aquaporins (AQPs), facilitate the changes of volume and shape, which additionally require a complex interplay between the plasma membrane and the cytoskeleton. AQPs have been shown to be involved in the development of inflammatory processes and diseases. The aims of the studies underlying this thesis were to further elucidate the expression and function of AQPs in both bacterial and viral infections as well as in the inflammatory disease, microscopic colitis. For this, molecular techniques qPCR, immunoblotting and live, holographic, confocal and super-resolution imaging were used. When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI- mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3OC12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages. Viruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections. Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC. Taken together, this thesis provides new evidence on the importance of water homeostasis regulation through AQPs during infections and inflammation and opens up a door for further investigations of roles for AQPs in inflammatory processes.
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Mertens, Kathrin. "Zinc in inflammation and sepsis". Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=204050.
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Sepsis is the major cause of mortality on intensive care units (ICU) with ~36,000 deaths annually in the UK. Sepsis is a systemic, dysregulated activation of the innate immune system in response to an infection characterised by excessive inflammatory mediator production and oxidative stress. Mitochondrial dysfunction is implicated in sepsis-‐induced organ dysfunction and death. Zinc is an essential micronutrient with a multitude of biological functions, including anti-‐inflammatory and antioxidant properties. A relationship has been established between zinc deficiency and severity of sepsis, in which zinc deficiency negatively influences the processes of sepsis leading to organ damage and ultimately death. This study investigated the effect of zinc on sepsis-‐related mechanisms to evaluate its importance for sepsis pathophysiology. The relationship between zinc levels and sepsis-‐related molecular mechanisms were investigated in an endothelial cell culture model of sepsis and in blood samples obtained from patients on ICU with and without sepsis. The in vitro study showed no evidence of zinc as an antioxidant or anti-‐inflammatory agent in endothelial cells exposed to lipopolysaccharide and peptidoglycan, however mitochondrial baseline function was increased in a zinc concentration-‐dependent manner. Plasma zinc levels were far below normal in all patients and patients with sepsis had lower levels compared to non-‐infected patients, possibly because they were overall more severely ill. No clear correlations could be established between plasma zinc and markers of inflammation, oxidative stress or disease severity. The lack of anti-inflammatory and antioxidant properties of zinc in the endothelial sepsis model, and the lack of clear correlations between zinc and markers of disease severity, inflammation and oxidative stress in the clinical study, challenges the concept of the importance of zinc in the pathophysiology of sepsis. The prolonged reduction of plasma zinc in all ICU patients prompts to consideration of zinc supplementation to replenish plasma levels and assure sufficient availability to maintain tissue functions.
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Barroso, Joana Barbara de Bessa. ""Obesity and inflammation: associated polymorphisms"". Master's thesis, Faculdade de Medicina da Universidade do Porto, 2008. http://hdl.handle.net/10216/23729.
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Cheong, Poh Yue. "Novel imaging targets in inflammation". Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/42989.
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Over the last two decades, research into the imaging of inflammation has been thoroughly investigated as it presents a promising therapeutic target for many diseases, including neurodegenerative and cardiovascular diseases. There are only a few radiopharmaceuticals which are currently in general use for imaging inflammation, e.g. 18F-FDG, nuclear labelled autologous white blood cells, 67Ga-citrate etc. However, none is specific for inflammation thus there is a need to investigate novel imaging agents for distinguishing sterile inflammation from infection. Formyl peptide receptors (FPRs) were originally identified as chemoattractant receptors, which have been shown to be implicated with potential therapeutic benefits for inflammatory diseases. Highly specific hexapeptides, cFLFLFK (cinnamoyl-Phe-D-Leu-Phe-D-Leu-Phe-Lys-NH2) and WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met-NH2), which are selective antagonist and agonist for FPR1 and FPR2 respectively, have been modified by conjugating to a cyclen based chelate for metal ions, allowing for specific imaging of inflammation using non-invasive imaging techniques such as MRI, PET and SPECT. This thesis depicts the synthesis of a bifunctional chelate, DOTAGA containing five acetate arms. Ln.DOTAGA-conjugates were prepared by coupling the Ln(III) complexes of DOTAGA onto the desired peptides without a protection step as the four pendant acetate arms were involved in coordination. Their binding affinities and biological functions were assessed by various in vitro assays such as radioligand binding assays, chemotaxis and TNF-α induced cytokine release. In vivo imaging of inflammation using the synthesised compounds and a mu-rine model of inflammation was performed. Further to this, the DOTAGA was further modified to an anhydride analogue, which allows for post radiolabelling after conjugation to the peptides. Subsequent complexation with Cu(II) and Ga(III) ions indicated their potential use in nuclear imaging. Two organic chromophores based on Cy5 bearing two orthogonal functional groups have been synthesised. Successive conjugation with cFLFLFK and confocal microscopy indicated their potential use in optical imaging. Multimodal imaging agents featuring a Cy5 chromophore and a DOTAGA for inflammation have been designed and synthesised. Subsequent complexation with Gd(III) and Tb(III) resulted in MRI/optical and dual luminescent imaging agents, respectively.
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de, Sá Pereira Inês Tavares Pinto. "Developmental response to brain inflammation". Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:3c1a3270-4eff-42bb-866c-716a9ad30a96.
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Perinatal inflammation contributes to neurodevelopmental diseases, and animal models have revealed that the inflammatory response within the central nervous system is age dependent. It remains unclear what intrinsic and/or extrinsic factors are responsible for this variation. Here, my aim was to discover the mechanisms responsible for the age-dependent changes in the inflammatory response of the brain by injecting interleukin-1 (IL-1β) into the brain of mice at postnatal day (P)7, P14, P21 or into adult mice. A "window of susceptibility" was found at P14, which was associated with marked neutrophil recruitment and blood-brain barrier (BBB) breakdown, in response to a low dose of IL-1β. Evaluation of cytokine, chemokine, and adhesion molecule mRNA transcripts failed to reveal any specific increases in basal or reactive expression following the injection of IL-1β at P14. The extrinsic hepatic acute phase response (APR) was evaluated, but, once again, there was no evidence that an altered APR might account for the enhanced inflammatory response at P14. Indeed, an inverse relationship between the magnitude of the leukocyte recruitment to the brain and the APR was discovered. Enhancement of the APR with intravenous IL-1β after injection of a low dose of IL-1β into the brain was found to reduce the number of neutrophils and BBB permeability in the brain. While no molecular changes seem to account for the presence of the "window of susceptibility", a population of Iba-1+ large, flattened and irregular perivascular cells was discovered within the P14 brain, that may contribute to the increased leukocyte recruitment at P14. Although variations in the brain inflammatory response with development were not fully account for, my results highlight the importance of the systemic inflammatory response on the outcome of acute brain injury and suggest that the systemic APR might be manipulated therapeutically to protect the brain in the perinatal period.
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Wardlaw, Andrew. "Studies on asthma and inflammation". Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/47294.
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Warland, D. A. "Inflammation, the microcirculation & microalbuminuria". Thesis, Exeter and Plymouth Peninsula Medical School, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.701316.
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Charteris, David Graham. "T lymphocytes in intraocular inflammation". Thesis, University of Edinburgh, 1994. http://hdl.handle.net/1842/19619.
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Pathological and immunohistochemical analyses of two forms of human intraocular inflammatory disease, multifocal posterior uveitis and Behcet's disease, were carried out. Studies of post-mortem eyes from a patient with multifocal posterior uveitis revealed a focal lymphocytic infiltrate in the choroid, extending through Bruch's membrane to the retina. Endothelial cells of choroidal vessels at the inflammatory foci had the morphological appearance of "high endothelial venules" known to be involved in the selective trafficking of lymphocytes. Immunohistochemical analysis of the lymphocytic infiltrate showed that 70-80% were T cells. Immunohistochemical analysis of enucleated and post-mortem eyes from Behcet's disease patients showed that the mixed leukocytic infiltrate found in the retina and uveal tract was composed predominantly of T lymphocytes and macrophages. The retinal vessels were hyalinised and narrowed in the post-mortem material and were noted to have IL2 receptor positive T lymphocytes in their walls. Aberrant expression of MHC class II antigens by organ-resident cells in these studies was minimal. Experimental work on an animal model of intraocular inflammatory disease, experimental autoimmune uveoretinitis, was undertaken to determine the in vivo lymphokine production of T lymphocytes in inflammatory eye disease. The T lymphocyte infiltrate in active EAU was identified immunohistochemically as was interferon-γ protein and IL2 receptor positive cells. cDNA probes specific for rat interferon-γ, IL2, lymphotoxin and IL4 mRNA were amplified, extracted and radiolabelled. These probes were used to identify autoradiographically mRNA for these lymphokines in the destructive tissue pathology in EAU using the technique of in situ hybridisation.
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Moran, Gordon William. "Enteroendocrine peptides in intestinal inflammation". Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/enteroendocrine-peptides-in-intestinal-inflammation(340b8b63-3b70-4ddd-bbce-4c9ab3e593cc).html.
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Introduction: Appetite is often impaired in patients with gastrointestinal inflammation. Up to 75% of hospitalised Crohn's disease (CD) patients are malnourished. Recent animal research has suggested that immune mediated upregulation of enteroendocrine cell (EEC) activity plays a mechanistic role in the appetite and feeding disturbance observed during gut inflammation. The role of EEC in producing factors regulating satiety and intestinal growth is well recognised but work on their use as therapeutic targets or agents in inflammatory bowel disease (IBD) is still in its infancy. EEC peptide dynamics are further controlled through dipeptidyl peptidase (DP4) protease metabolism but no data are yet available on its expression in IBD. My aim is to understand the roles of EEC in appetite control and the maintenance of gut mucosal integrity in intestinal inflammation. Methodology: Patients with CD and healthy controls were studied. Symptoms were assessed using visual analogue scores (VAS). Gut hormone responses to a test meal were studied using a multiplex-ELISA technique, and correlated to symptoms. At the tissue level, EEC markers and transcription factors were quantified using immunohistochemistry, quantitative polymerase chain reaction (qPCR) and western blotting techniques. The same techniques were used to study DP4 expression. The effects of glucagon-like peptide-2 (GLP-2) on a gut model of the epithelial barrier were studied by measuring the transepithelial electrical resistance (TEER) across GLP-2 exposed Caco-2 cell monolayers after cytokine exposure. Tight junction protein expression in naïve and GLP-2 exposed cells was quantified by western blotting. Main Results: CD patients with active inflammation displayed a significant reduction in appetite. At the tissue level, GLP-1 and chromogranin A (CgA) were significantly upregulated. At the mRNA level significant increased expression was noted for CgA, glucagon-like peptide-1 (GLP-1), ubiquitination factor 4a and neurogenin 3. At the plasma level, total polypeptide YY (PYY) was increased. A significant correlation was seen between postprandial PYY responses and symptoms of nausea and bloating. Ghrelin, was 3-fold higher in the CD group compared to controls, and showed a reversed postprandial response with a significant correlation with the CD activity index (CDAI). Protein DP4 expression was significantly decreased at the tissue and plasma level in CD. GLP-2 increased tight junction protein expression in Caco-2 cells and maintained stable TEER and tight junction protein expression after cytokine exposure. Conclusions: The data presented are compatible with a potential role of EEC in appetite dysregulation in intestinal inflammation. An enhanced EEC response to food intake may directly affect appetite in such patients through increased gut-brain signalling. These may present tractable therapeutic targets. The decrease in mucosal DP4 expression in CD may make bioactive GLP-2 more available in the affected gut, hence improving gut mucosal integrity in intestinal inflammation. This pilot work has shown that GLP-2 has a role in maintaining gut mucosal integrity in intestinal inflammation through a positive effect on tight junction protein expression.
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Kim, Sangmi Sandler Robert Samuel. "Obesity, inflammation and colorectal neoplasia". Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,2164.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Feb. 26, 2009). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Epidemiology, School of Public Health." Discipline: Epidemiology; Department/School: Public Health.
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Vallejo, Abigail. "Inhibition of SAA-mediated inflammation". Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/23011.
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The acute phase protein serum amyloid A (SAA) is a biomarker for acute inflammation, however there is growing evidence to suggest that this protein has bioactivity that contributes to the inflammatory process in disease states such as atherosclerosis whereby endothelial dysfunction is initiated. The data generated in this thesis shows that SAA can elicit the production of pro-inflammatory cytokines such as tumour necrosis factor (TNF), tissue factor (TF), interleukin-6 from human endothelial cell lines. The downstream molecular pathways of SAA is a well-characterised series of pro-inflammatory mediators involving the canonical transcription factor NFкB. pathways involving the canonical transcription factor NFкB pathway. Upon direct inhibition of NFкB using a pharmacological inhibitor (BAY11-7082), significant downregulation of pro-inflammatory genes and corresponding proteins was demonstrated. However, translation of the drug into clinical use is hampered by serious side effects. Therefore, alternative targets to the downstream pathway of SAA activation were also inhibited. Firstly, we attempted to use an endogenously expressed HDL, a lipoprotein that is proposed to ameliorate SAA bioactivity. That data generated appeared to be paradoxical and HDL was unable to act as a “molecular mop” to inhibit SAA activity. Further studies aimed to target reactive oxygen species (ROS) using a nitroxide which is a ROS scavenger. We provided proof of principle that the nitroxide TEMPOL was able to scavenge SAA-induced ROS. Further work will be required to validate the vaso-protective activity of the nitroxide class of drugs. If proven this may offer an alternative/adjunctive therapy for vascular inflammation elicited by SAA.
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Barroso, Joana Barbara de Bessa. ""Obesity and inflammation: associated polymorphisms"". Dissertação, Faculdade de Medicina da Universidade do Porto, 2008. http://hdl.handle.net/10216/23729.
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Weidmann, Rolf Günter. "Endothel und Regulation der Inflammation". Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/15424.
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Die durch Lipopolysaccharid (LPS) induzierte frühe Immunantwort ist ein wesentlicher Mechanismus der Infektabwehr durch die angeborene Immunität. Bei starker LPS-Exposition kann es andererseits zur Ausbildung eines septischen Syndroms kommen. Der endothelialen Sekretion von Interleukin-8 (IL-8/CXCL8), das als Chemokin die Migration neutrophiler Granulozyten vermittelt, kommt dabei herausragende Bedeutung zu. Zielsetzung dieser Arbeit war es, die Relevanz der Rho-Proteine RhoA, Rac1 und Cdc42 für die LPS-induzierte intrazelluläre Signaltransduktion mittels Überexpression inaktiver Mutanten dieser Proteine zu untersuchen. Diese Untersuchung wurde erschwert durch die schlechte Transfizierbarkeit der Endothelzelllinie HPMEC-ST1.6R, die nahezu alle Charakteristika primärer Endothelzellen aufweist. Deshalb wurde eine Methode etabliert, die durch Kotransfektion des Grünen Fluoreszenzproteins (GFP) die flusszytometrische Selektion der transfizierten Zellen anhand ihrer GFP-bedingten Fluoreszenz und die Messung der Expression von CXCL8 allein in dieser Population ermöglicht. Damit wurde nachgewiesen, dass die inaktiven Mutanten RhoAN19, Rac1N17 und Cdc42N17 jeweils die LPS-induzierte Expression von CXCL8 vermindern. Die größte Reduktion der CXCL8-Expression um 38 % der Positivkontrolle zeigte sich nach Transfektion der Mutante Rac1N17. Die Zelllinie CHO-3E10 exprimiert einen artifiziellen Reporter unter der Kontrolle eines Fragments aus der Verstärkerregion des Gens für das Endotheliale Leukozyten-Adhäsionsmolekül ELAM-1 (CD62E). Die Transfektion jeder einzelnen der inaktiven Varianten der drei GTP-bindenden Proteine in Zellen der Linie CHO-3E10 reduzierte die Expression des Reporterproteins nach Stimulation mit LPS signifikant. Die stärkste Reduktion der Reporterexpression um 51 % der Positivkontrolle ergab sich unter Rac1N17. Zusammengefasst zeigt die Studie, dass die Überexpression der inaktiven Mutanten RhoAN19, Rac1N17 und Cdc42N17 zu einer Abnahme der endothelialen Expression von CXCL8 führt. Darüberhinaus ergab sich im Vergleich zu den Mutanten RhoAN19 und Cdc42N17 die stärkste Reduktion der CXCL8-Expression in Endothelzellen nach Transfektion der Mutante Rac1N17.The early immune response induced by Lipopolysaccaride (LPS) is a crucial mechanism in fighting off infections by the innate immunity. On the other side high amounts of LPS can lead to the development of a sepsis. In this process the endothelial secretion of interleukin-8 (IL-8/CXCL8), which causes the migration of neutrophilic granulocytes to the site of infection is highly important. The aim of this study was to analyze the relevance of each of the three Rho-proteins RhoA, Rac1 and Cdc42 for the intracellular signal transduction resulting in CXCL8-expression by means of overexpressing inactive mutants of these proteins. Cells of the human microvascular endothelial cell line HPMEC-ST1.6R show most characteristics of primary endothelial cells and are extremely difficult to transfect. Therefore a method was established, which allowed sorting of successfully transfected cells by cotransfecting a gene encoding for green fluorescence protein (GFP). This method permitted measuring intracellular expression of CXCL8 in the population successfully transfected with plasmids encoding for RhoAN19, Rac1N17 or Cdc42N17 mutants. This experiments demonstrated that the inactive mutants RhoAN19 Rac1N17 or Cdc42N17 each decreased the LPS-induced expression of CXCL8. Quantitative comparision showed the greatest reduction of 38 % in CXCL8-expression due to transfection of the Rac1N17 mutant. The LPS-inducible reporter cell line CHO-3E10 used in this study expresses the human CD25-antigene as an artificial reporter protein under the control of a fragment from the enhancer region of the gene for the human endothelial leukocytic adhesionmolecule ELAM-1 (CD62E). Transfecting each of the inactive mutants RhoAN19, Rac1N17 or Cdc42N17 in CHO-3E10 cells significantly reduced the LPS-induced expression of the reporter protein. The greatest reduction in reporter expression of 51 % resulted from transfection with the Rac1N17 mutant. In conclusion, this study demonstrates that overexpression of nonfunctional GTP-binding proteins RhoAN19, Rac1N17 or Cdc42N17 leads to a decrease in endothelial CXCL8-expression. Moreover, CXCL8-expression in endothelial cells transfected with the Rac1N17 mutant was most efficiently reduced when compared to the other mutants.
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Chen, Shao Ru. "Andrographolide analogues inhibit acute inflammation". Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3953265.
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