Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 77-90).

Thesis (M.A.)--University of North Carolina at Chapel Hill, 2005. / Includes bibliographical references (leaves 45-51). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.A.)--University of North Carolina at Chapel Hill, 2005. / Includes bibliographical references (leaves 45-51).

Thesis (Ph.D.)--Baylor University, 2009. / Includes bibliographical references (p. 107-129).

Orientador: Raphael Lucio Andreatti Filho / Coorientador: Adriano Sakai Okamoto / Banca: Raphael Lucio Andreatti Filho / Banca: Angelo Berchieri Junior / Banca: Ivens Gomes Guimarães / Resumo: Tendo em vista a variedade de funções da serotonina e poucos estudos em aves sobre o tema, o presente trabalho teve como objetivo avaliar os efeitos da serotonina, através do seu precursor (5-hidroxitriptofano) e seu inibidor (m-hidroxibenzilhidrazine), associados à Lactobacillus spp. na resposta imune e na morfometria intestinal de frangos de corte desafiados com Salmonella Enteritidis. A partir da avaliação do comportamento e peso corporal das aves, estabeleceu-se a dose do precursor (5HTP), da serotonina, e do inibidor (NSD1015). Com a dose definida, o estudo foi dividido em dois experimentos, aves sem desafio com S. Enteritidis e aves com desafio. Avaliou-se a resposta imune humoral das aves através das concentrações de IgA no fluido intestinal e IgG no soro sanguíneo e recuperação de S. Enteritidis no conteúdo cecal. A morfometria intestinal foi determinada por meio da avaliação do peso corporal, número e altura das vilosidades no duodeno, e, a disponibilidade de serotonina no duodeno foi observada por ensaios imunoistoquímicos. Serotonina ocasionou alterações caracterizadas por sonolência e diminuiu o ganho de peso das aves. Seu precursor (5HTP) também ocasionou sonolência nas aves, porém em intensidade menor e o ganho de peso foi mantido. As aves em que o inibidor (NSD1015) foi administrado não apresentaram alterações no comportamento e ganho de peso. O precursor, inibidor e Lactobacillus spp. não influenciaram nas concentrações de IgA e IgG, mas o precursor e Lactobacillus spp. reduziram a quantidade de S. Enteritidis no conteúdo cecal. Com relação à morfometria intestinal, as aves tratadas com 5HTP apresentaram aumento no peso corporal, no número e altura das vilosidades no duodeno. Lactobacillus spp. e S. Enteritidis determinaram a elevação de células que imunoexpressaram serotonina no duodeno. Os resultados obtidos nos mostram uma possível interação do precursor e ... / Abstract: Given the variety of functions of serotonin and few studies in birds on the topic, this study aimed to evaluate the effects of serotonin, through its precursor (5-hydroxytryptophan) and its inhibitor (m-hidroxibenzilhidrazine) in association with Lactobacillus spp. in the immune response and the intestinal morphometric of broiler chickens challenged with Salmonella Enteritidis. From the evaluation of the behavior and body weight of the birds, established the dose of the precursor (5HTP), serotonin, and inhibitor (NSD1015). With a defined dose, the study was divided into two experiments, birds without challenge with S. Enteritidis and birds challenge. We evaluated the humoral immune response of the birds by the concentrations of IgA in intestinal fluid and the blood serum IgG recovery and S. Enteritidis in cecal contents. The intestinal morphology was determined by evaluating the weight, number of villi and duodenal villus height, and the availability of serotonin in the duodenum was observed by immunohistochemical assays. Serotonin induced changes characterized by drowsiness and decreased weight gain of birds. Its precursor (5HTP) also caused drowsiness in birds, but at a lower intensity and weight gain was maintained. And the birds in the inhibitor (NSD1015) was administered showed no changes in behavior and weight gain. The precursor, inhibitor and Lactobacillus spp. did not affect the concentrations of IgA and IgG, but the precursor and Lactobacillus spp. reduced the number of S. Enteritidis in cecal contents. With regard to intestinal morphology, 5HTP-treated birds showed an increase in body weight, the number of villi and duodenal villus height. Lactobacillus spp. and S. Enteritidis determined the elevation of cells imunoexpressaram serotonin in the duodenum. The results suggested a possible interaction of the precursor and Lactobacillus, acting on the immune response and development of villi inestinais / Mestre

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.

No description available.

Primarily synthesised via cutaneous exposure to solar ultraviolet B (UVB) radiation, serum vitamin D concentrations, measured as 25-hydroxyvitamin D (25(OH)D), fluctuate according to solar availability. Seasonal variations in vitamin D are common in areas of high or low latitude determined by the distance from the sun. Seasonal variations in blood pressure, immune markers and some diseases including influenza, have also been reported. However, the contributions of UVB light or vitamin D on the immune markers have not been fully determined. Against this background, the purpose of this research was to investigate the effects of UVB light therapy and dietary vitamin D supplementation on markers of immune function. The D SIRe1 study aimed to assess whether dietary-derived 25(OH)D could have similar effects on immune function as light-derived 25(OH)D. The study was an 8-week comparative intervention trial in healthy adults randomised to receive either 3 times weekly UVB radiation (equivalent to doses received during a Grampian-summer) for 4 weeks; or oral vitamin D3 (1000 IU a day for 8 weeks). Total 25(OH)D was measured by dual tandem mass spectrometry of serum samples following removal of protein and de-lipidation, whilst regulatory T cells (Tregs), known for maintaining immune system homeostasis, by flow cytometry. The study showed similar short-term effects between oral vitamin D and UVB exposure on measured outcomes. However, study interpretation was limited by the lack of a placebo group, yet, to our knowledge, this was the first study to directly compare dose-matched UVB therapy and vitamin D supplementation in healthy participants. Using similar laboratory techniques, the D-SIRe2 study, a placebo-controlled trial, assessed short-term (12 weeks) and long-term (43 weeks) effects of vitamin D supplementation on immune markers. Commencing in spring (March) and finishing in winter (January) 2015/2016, the study showed seasonal fluctuations in most immune markers. The fluctuations did not change according to variations in 25(OH)D concentrations nor were they correlated with solar UVB doses, with the exception of T cell proliferative responses, which were positively correlated with daily solar UVB doses. An interesting finding from this study was the prevention of increases in pro-inflammatory IFN-γ cytokine concentrations in the spring and summer time in the vitamin D3 supplemental group versus placebo. IFN-γ concentrations were raised from 7940 pg/mL at baseline in March, to roughly 12400 pg/mL at week 4 and to 13909 pg/mL at week 12 in the placebo group. The concentrations were roughly 1.3 times the mean concentrations measured in the vitamin D group at the timepoints following baseline concentrations of 10678 pg/mL, and 10013 pg/mL and 10233 pg/mL at weeks 4 and 12, respectively. The interactions between solar light or seasonal effects and oral vitamin D supplementation, as well as their individual and combined effects on immune function, are yet to be fully determined. Moreover, the metabolic and physiological implications of seasonal variation in serum 25(OH)D concentration and markers of immune function are currently unknown, requiring further investigation.

The proposed thesis contributes to the knowledge about tick-borne encephalitis and its pathogenesis. The thesis describes pathogenesis and immunopathogenesis of tick-borne encephalitis, impact of host's genotype in clinical course determination, immune response of patients with acute tick-borne encephalitis, the mechanism of tick-borne encephalitis virus migration into central nervous system and virus interaction with cells of neurovascular unit as well as potential medical interventions.

Made available in DSpace on 2014-06-11T19:33:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-03-08Bitstream added on 2014-06-13T20:05:18Z : No. of bitstreams: 1 moreira_prr_dr_jabo.pdf: 7658386 bytes, checksum: 88b2f8c6da6bd4b4dede297970617c96 (MD5) / Na Leishmaniose Visceral Canina (LVC) a resposta imune órgãoespecífica pode variar de acordo com o órgão afetado, favorecendo ou não a multiplicação do parasito Leishmania (L.) chagasi. O objetivo deste estudo foi analisar, por meio, da técnica de imuno-histoquímica, o fígado e o baço de cães com Leishmaniose Visceral (LV), considerando a carga parasitária, a densidade de células Natural Killer (NK), de macrófagos e de linfócitos, bem como, células em apoptose, de células expressando moléculas de MHC-II e as citocinas TGF-b e TNF- a. Estes resultados foram comparados com os diferentes estágios da doença. Utilizou-se 71 cães naturalmente infectados de área endêmica para LV, classificados nos grupos sintomático (S), assintomático (A) e oligossintomático (O). Um grupo controle foi composto por 10 cães de área não endêmica para LVC. As células positivas para os anticorpos CD56, caspase 3 clivada, MHC-II, TGF- , TNF- , MAC387, CD3 e para a carga parasitária (soro hiperimune de cão positivo para LVC) foram submetidas a testes não paramétricos para a comparação entre os grupos. O baço foi o órgão que apresentou a maior carga parasitária. A apoptose de linfócitos foi maior nos cães sintomáticos quando comparados ao grupo controle. A intensidade de inflamação foi elevada nos cães com doença avançada (grupo S), caracterizada pela formação de granulomas difusos contendo parasitos. O fígado mostrou menor carga parasitária, um perfil celular dos granulomas rico em linfócitos. A densidade de células NK foi baixa no fígado e baço, bem como a imunodetecção das citocinas TGF- e TNF- . A expressão de MHC-II foi maior no baço de cães do grupo S. Portanto, pode-se sugerir que existe um padrão de resposta diferenciado no baço e fígado, porém outra metodologia deveria ser utilizada para quantificar de forma mais precisa as citocinas TGF- e TNF- nestes órgãos / In Canine Visceral Leishmaniasis (LVC), the immune response to organ-specific can vary with the affected organ, thus favoring or hindering the multiplication of the parasiteLeishmania (L.) chagasi. . The aim of this study was to analyze by immunohistochemistry, the liver and spleen of dogs with visceral leishmaniasis (VL), considering the parasitic load, the density of Natural Killer cells (NK), macrophages and lymphocytes, as well apoptosis cells, cells expressing molecules of MHC-II and the cytokines TGF- and TNF- . These results were compared with different stages of disease. We used 71 naturally infected dogs from an endemic area for VL, classifieds in the symptomatic (S), asymptomatic (A) and oligosymptomatic (O) groups. A control group consisted of 10 dogs from nonendemic area for LVC.The positive cells for CD56 antibody, cleaved caspase 3, MHC-II, TGF- , TNF- , MAC387, CD3 and parasite load (serum hyperimmune dog seropositive for VL) were subjected to nonparametric tests for comparison between groups. The spleen was the organ with the highest parasite load. The apoptosis of lymphocytes was higher in symptomatic dogs when compared to the control group. The intensity of inflammation was higher in dogs with advanced disease (group S), characterized by the formation of granulomas containing diffuse parasites. The liver showed lowest parasite load, a profile of cell granulomas rich in lymphocytes The density of NK cells was low in the liver and spleen and few cells were positive for cytokines TGF- and TNF- . Expression of MHC-II was higher in the spleen of dogs in Group S. Therefore, one may suggest that there is a differential pattern of response in the spleen and liver, but other methods should be used to quantify more accurately the cytokines TGF- and TNF- in these organs