Thesis (Ph. D. in Mathematics)--Vanderbilt University, Aug. 2007. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 69-82).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 163-183).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 152-176).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 158-183).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 137-169).

Th. 3e cycle--Physiol. de la nutr.--Toulouse 3, 1977. N°: 1997.

Made available in DSpace on 2014-06-11T19:30:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-01-20Bitstream added on 2014-06-13T18:40:48Z : No. of bitstreams: 1 goncalves_a_dr_jabo.pdf: 482879 bytes, checksum: 0e902aebca008cecff34c13a46883198 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / Este trabalho avaliou o efeito de dietas contendo probiótico e espirulina sobre a formação de macrófagos, variáveis hematológicas e bioquímicas em tambaqui Colossoma macropomum jovens mantidos em duas densidades de estocagem. Previamente foi conduzido por três meses com três dietas alimentares - grupo controle, probiótico e espirulina; utilizando três caixas de água com capacidade de 500 L em sistema aberto de produção com renovação de água e filtragem biológica. Posteriormente, o experimento teve a duração de 12 dias, utilizando 36 caixas plásticas com capacidade de 50 L, com aeração e renovação de água constantes. O delineamento experimental foi inteiramente casualizado em um esquema fatorial 3 x 2 x 2 (dietas x densidade de estocagem x lamínulas), totalizando em 12 tratamentos, onde cada tratamento apresentava um grupo com peixes implantados lamínulas (I) e outro grupo com peixes sem implantes de lamínulas (S), apresentando três repetições cada, sendo: T1 – ração controle com densidade 5 kg/m3 com (I) e (S); T2 – 1g probiótico/kg ração com densidade 5 kg/m3 com (I) e (S); T3 – 5g espirulina/kg ração com densidade 5 kg/m3 com (I) e (S); T4 – ração controle com densidade 20 kg/m3 com (I) e (S); T5 – 1g probiótico/kg ração com densidade 20 kg/m3 com (I) e (S); T6 – 5g espirulina/kg ração com densidade 20 kg/m3 com (I) e (S). Foram coletados dois indivíduos por tratamento, nos intervalos de 0, 3, 7, 10 e 12 dias experimentais para avaliação das variáveis hematológicas, bioquímicas e contagem dos núcleos das células gigantes. Os resultados mostraram que a suplementação da dieta de tambaqui com probiótico ou espirulina não causaram alterações nos valores hematológicos, bioquímicos e na formação de célula gigante. Contudo, ocorreu maior... / The aim of this experiment was to evaluate the effect of diets contend probiotic and spirulina on small glass blades implanted, hematological and biochemistry parameters of tambaqui, Colossoma macropomum, juveniles, submitted the two different stockage density. The pay-experimental period was lead by three months with three alimentary diets – control group I, group contend probiotic in diet and group contend spirulina in diet; three boxes were used in a 500 L water capacity, in open system of production with water renewal and biological filtering. After, the experiment had the duration of twelve days; thirty six plastic boxes were used in a 50 L, with aeration and constant water renewal. The experimental design was a factorial design - 3 x 2 x 2 (diets x stockage density x small glass blades), totalizing in twelve treatments, presented a group with small glass blades implanted fish (I) and another group with fish without implantations of small glass blades (S), with three repetitions each, being: T1 - ration has controlled in density 5 kg/m3 with (I) and (S); T2 - ration contend 1g probiotic/kg in density 5 kg/m3 with (I) and (S); T3 - ration contend 5g spirulina/kg in density 5 kg/m3 with (I) and (S); T4 - ration has controlled in density 20 kg/m3 with (I) and (S); T5 - ration contend 1g probiotic/kg in density 20 kg/m3 with (I) and (S); T6 – ration contend 5g spirulina/kg in density 20 kg/m3 with (I) and (S). Were collected two fish for treatment, in the intervals of 0, 3, 7, 10 and 12 experimental days for evaluation of the hematological and biochemistry parameters, and counting of giant cells nucleus. The results had shown that the diet supplemented of with probiotic and spirulina had not caused alterations in the hematological and biochemistry parameters and in the formation of giant cell o tambaqui. However... (Complete abstract click electronic access below)

NAD+ has previously been shown to regulate TNF-α synthesis and TNF-α has been shown to regulate NAD+ homeostasis, thus providing a link between a pro-inflammatory response and redox status. Despite the well-established link between TNF-α and NAD+, the mechanism as to how NAD+ modulates TNF-α release is not fully understood. To achieve this, this link was investigated using THP-1 cell line-derived M1-like (pro-inflammatory) and M2-like (anti-inflammatory) macrophages using PMA and vitamin D3, respectively. NAD+ levels differed markedly between M1-like and M2-like macrophages, with M1-like having much higher basal levels. LPS increases NAD+ levels and TNF-α secretion in M1-like but not M2-like cells. In an effort to investigate the source of the NAD+ levels and the association with TNF-α release, three inhibitors (FK866, DPI and 1D-MT) were used. Following stimulation, NAD+ is produced partially via NADH oxidation and partially through NAD+ synthesis. Both DPI and FK866 reduced TNF-α secretion with DPI showing the largest effect. The two phenotypes showed differential profiles of NAD+ homeostasis gene expression compared with each other and with the progenitor THP-1 in both resting and activated states. While IDO expression was induced in both phenotypes, CD38 and NAMPT were upregulated in M1-like cells whereas CD157 was upregulated in M2-like cells. LPS induced M1-like cells to up-regulate CD38 and CD157 and down-regulate NAMPT unlike M2-like cells which up-regulated NAMPT and CD38 and down-regulated CD157. M1s increased glycolysis activity whereas conversely, decreased oxidative metabolism during LPS stimulation confirming previous findings showing that classical M1s are predominantly glycolytic. Collectively, these data suggest that the relationship between NAD+ levels and pro-/anti-inflammatory responses is complex and may be regulated via a combination of pathways. These findings open the possibility of pharmacological manipulation of NAD+ synthesis as a way of selectively modulating macrophage responses which may be beneficial for the development of therapeutics targeting inflammatory diseases.

Gut-associated lymphoid tissues such as Peyer’s patches (PP) are inductive sites for immune response in the intestine. Unlike other peripheral lymphoid tissues, gut-associated lymphoid tissues lack afferent lymphatics and can directly sample mucosal antigens by specialized epithelial cells in the follicular associated epithelia (FAE), known as M cells. M cells derive from Lgr5+ intestinal stem cells in intestinal crypts, where the daughter cells of Lgr5+ cells differentiate into M cells after stimulation from the cytokine receptor activator of nuclear factor-κB ligand (RANKL). RANKL is produced by stromal cells within the sub-epithelial dome (SED) residing below the FAE. The transcytosis of antigens across the FAE by M cells is an important initial step in the induction of efficient mucosal immune responses against certain pathogenic bacteria as well as the commensal bacterial flora. However some pathogens, for example orally-acquired prions, may also exploit M cells to infect the host. M cells have been implicated in the uptake of orally acquired prions from the gut lumen. After oral exposure, the accumulation of prions in PP is important for their efficient spread to the nervous system. Previous studies have also shown that pathogen-induced inflammation increases M cell density and this effect can be mimicked by exogenous administration of RANKL. This has led to the hypothesis tested in this thesis that inflammation-related enhancement of M cell differentiation aids the delivery of prions into the lamina propria of villi. The administration of RANKL resulted in increased M cell density in the gut epithelium of mice. Consequently, RANKL treatment enhanced the accumulation of orally-administered prions in PP, decreased disease incubation time and increased prion disease susceptibility. These data indicate the importance of M cells in prion disease pathogenesis and highlight the potential of M cells as vaccine targets against prion disease. The fate and terminal differentiation of distinct intestinal epithelial cell lineages from their uncommitted precursors is dependent on their intrinsic expression of one or more specific transcription factors during their development. Alongside inducing M cell differentiation, RANKL stimulation can also induce the nuclear translocation of the NF-κB transcription factor subunit c-Rel. A comparison of the genes encoding the individual NF-κB subunits c-Rel, Rel-A and Rel-B revealed that they were expressed at the mRNA level in the FAE and by M cells. A c-Rel-deficiency in mice did not influence the expression of RANKL or RANK in PP. The subsequent induction of M cell maturation in the FAE was also unaffected in, indicating that c-Rel is dispensable for the RANKL-mediated differentiation and functional maturation of M cells. The factors implicated in Lgr5+ intestinal stem cell proliferation and their differentiation into M cells are poorly understood. Some reports have indicated that crypt-associated macrophages may provide extrinsic factors that assist Lgr5+ intestinal stem cell proliferation. In this thesis, the ablation of macrophages in the gut resulted in dysregulation of crypt microarchitecture, depleting Paneth cells and the Lgr5+ stem cells. This adversely affected the subsequent differentiation of intestinal epithelial cell lineages and impeded the functional development of M cells. These data reveal a previously unknown role for macrophages in the maintenance of intestinal crypts and intestinal stem cell proliferation and differentiation.