Os linfócitos T sofrem rígida regulação homeostática desde seu desenvolvimento até sua maturação, expansão clonal e morte celular. Compostos endógenos ou exógenos que alterem as funções fisiológicas dos linfócitos T podem modular passos importantes da resposta imune. Triptofano tem um papel importante na manutenção da homeostasia dos linfócitos T e é o precursor da síntese de melatonina. Neste estudo, avaliamos os efeitos de triptofano, melatonina e seus produtos de oxidação sobre os principais processos de ativação e desativação dos linfócitos T. Inicialmente, investigamos os efeitos biológicos de L-quinurenina (KYN, composto formado na via de metabolização do triptofano), melatonina e seus produtos de oxidação N1-acetil-N2-formil-5-metoxiquinuramina (AFMK) e N1-acetil-5- metoxiquinuramina (AMK) sobre a proliferação dos linfócitos T humanos e na produção de interferon-gamma (IFN-γ) e das interleucinas IL-2, IL-10 e IL-12. Observamos que KYN, melatonina, AFMK e AMK inibem a linfoproliferação e a liberação de IL-2 e de IFN-γ . O efeito inibitório destes compostos na síntese de IFN-γ não está associado às variações na produção das duas citocinas mais importantes na regulação de IFN-γ , ou seja, IL-10 e IL-12. Na seqüência, descrevemos a ação da melatonina e seus produtos de oxidação, sobre a morte celular induzida por ativação (AICD) de hibridomas de linfócitos T e os possíveis mecanismos de ação. Os resultados deste estudo mostram que tanto melatonina quanto AFMK e AMK são potentes inibidores da apoptose dos linfócitos T. Estes compostos inibem a ativação do Fator de Transcrição Nuclear de Células T ativadas (NFAT) e suprimem a expressão da molécula Fas Ligante (FasL), que é o evento imprescindível para a indução da AICD. Como conclusões, verificamos que os produtos formados tanto a partir da oxidação de triptofano quanto de melatonina são potenciais reguladores da resposta imune e podem participar dos efeitos imunossupressores, nos quais a depleção de triptofano tem sido sugerida como principal mecanismo de regulação dos linfócitos T. Adicionalmente, nossos achados podem ter utilidade na avaliação de possíveis efeitos indesejáveis durante a utilização terapêutica de melatonina. / T Lymphocytes are exposed to severe homeostatic regulation from development stage up to their maturation, clonal expansion and cell death. Endogenous or exogenous compounds altering the physiological functions of T lymphocytes can modulate important steps of the immune response. Tryptophan plays an important role for maintaining the homeostasis of T lymphocytes and is the precursor of the melatonin synthesis. In this study we evaluated the effects of tryptophan, melatonin and their oxidation products concerning the main activation and deactivation processes of T lymphocytes. Firstly, we analyzed the biological effects of L-kynurenine (KYN, a compound formed at the tryptophan metabolization pathway), melatonin and its oxidation products, N-acetyl-N-formyl-5-methoxykynuramine (AFMK) and N-acetyl-5- methoxykynuramine (AMK), concerning the proliferation of human T lymphocytes and the production of interferon-gamma (IFN-γ) as well as of interleukins IL-2, IL-10 and IL-12. It was observed that KYN, melatonin, AFMK and AMK inhibit the lymphocytes proliferation and the release of IL-2 and IFN-γ. The inhibitory effect of these compounds in the IFN-γ synthesis is not related to the variations on the production of the two most important cytokines for the IFN-γ regulation, that is, IL-10 and IL-12. After that, we reported the melatonin action as well as of its oxidation products, in what concerns activation-induced cell death (AICD) of T lymphocytes hybridomas and probable activation mechanisms. The results of this study have shown that melatonin as well as AFMK and AMK are powerful inhibitors of the T lymphocytes apoptosis. These compounds inhibit the activation of the nuclear transcription factor of activated T cells (NFAT) and suppress the expression of the Fas-Ligand molecule (FasL), which is the essential event to the AICD induction. We concluded that products formed by the oxidation of either tryptophan or melatonin are potential regulators of the immune response and may participate on immunosuppression effects, in which the tryptophan depletion is believed to be the main mechanism for T lymphocytes regulation. Added to that, our results may be helpful for evaluating possible unwanted effects during the therapeutical use of melatonin.

The objective of this study was to examine the potential effects of supplementing excess crystalline tryptophan (trp) in the lactation diets of sows. Sixty-one sows of varying parity were fed either a control diet (0.26% trp) or a treatment diet with an extra two grams of tryptophan (0.30% trp). Over the 28 day lactation period utilized by the production site, sow and litter performance were recorded. Sow performance was measured by backfat loss, blood urea nitrogen, milk composition, return to estrus, wean to estrus interval, and conception rate. Litter performance was measured as average weaning weight, number weaned, and pre-wean mortality. The control and treatment groups were further subdivided by parity for statistical analysis. Sows of parity one and two were classified as primiparous, while sows of parity three or more were classified as multiparous. There were no significant differences (P≤0.05) between the control and treatment diets even with regards to parity groups. There was one trend (0.05 0.10) in which treatment multiparous sows had higher litter weaning weight (P=0.055) than the control multiparous sows. In summary, these results indicate that increasing the tryptophan level in this lactation diet by two grams did not significantly influence sow or litter performance.

Animal agonistic behaviors, including threat, combat, submission and chase, are complex responses to experimental stimuli. Animal behaviors are regulated by the central nervous system. In the central nervous system, the biogenic amine serotonin has been thought to serve important roles in animal aggression (including fish), but it¡¦s not clear if serotonin affects threatening and fighting differently. This study took experimental approaches to examine the effects of this neurotransmitter on threatening and fighting in a paradise-fish model in which the complex agonistic behavior is well characterized. Treatments with serotonin synthesis precursor tryptophan (0.125mg/g) to one of the two contestants had insignificant effects on threatening or fighting while synthesis blocker p-Chlorophenylalanine (PCPA) (0.3mg/g) decreased threatening time and occurrences of head-tail display. When these drugs were added to both contestants, tryptophan reduced all agonistic behavioral patterns displays, and PCPA decreased threatening time and head-tail display. In addition to changes in behavioral patterns, tryptophan led the fish to be attacked. In contrast, PCPA led the injected fish to actively attack its opponent. However, tryptophan and PCPA had no effect on social status in parasise fish. I suggest that agonistic responses and the initial fighting decision in a paradise fish are affected not only by level of its serotonin, but also by the behavioral responses of its opponent. And the establishment of outcome of encounter is affected more by the environmental stimuli than the serotonin level.

published_or_final_version / Chinese Medicine / Master / Master of Philosophy

No description available.

Amadori rearrangement product (ARP) of tryptophan with glucose was synthesized according to a published procedure, and its decomposition was studied at two different concentrations and at two temperatures, 110$ sp circ$C and 140$ sp circ$C over a period of 6 hrs. A RP-HPLC system was developed to separate and quantitate the decomposition products of the ARP. The results indicated that, the ARP can decompose to form the following products, hydroxymethylfurfural (HMF), maltol, indole, $ beta$-carbolines (norharman and harman) and tryptophan. Further, using the same analytical method, the following systems were also analyzed for the presence of the above mentioned products (a) D-glucose and D-mannose with tryptophan; (b) D-glucose; and (c) tryptophan. In addition, rate constants and activation energies for the decomposition and formation reaction were calculated. Plausible mechanisms for the formation of the decomposition products are suggested.

No description available.

Zugl.: Giessen, Univ., Diss., 2007

Thesis (Ph. D.)--University of Wisconsin--Madison, 1957. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 157-172).

Universiẗat, Diss., 2007--Giessen.