Proefschrift--Amsterdam.

Thèses (M.Sc.)--Université de Sherbrooke (Canada), 2001. / Titre de l'écran-titre (visionné le 20 juin 2006). Publié aussi en version papier.

Thesis (Ph. D.)--University of Hawaii at Manoa, 2002. / Includes bibliographical references (leaves 106-116). Also available on microfiche.

Thesis (Ph. D.)--University of Virginia, 1997. / Spine title: Mammalian DNA replication initiation. Includes bibliographical references (219-245). Also available online through Digital Dissertations.

<p> DL-Mimosine has been synthesized by debenzylation and detosylation of the product obtained by condensation of 3-benzyloxy-4-pyrone with β-amino-α-tosylaminopropionic acid. A new method for the isolation of mimosine from Leucaena glauca Benth. is described. The biosynthesis of mimosine was studied by feeding radioactive aspartates, glycerol, glycerate and ribose to Mimosa pudica L. . Mimosine-C^14 was isolated and partially degraded, and it was shown that the carbon-3 of aspartic acid is specifically incorporated into the pyridone ring.</p> / Thesis / Doctor of Philosophy (PhD)

A Leucaena leucocephala, popularmente conhecida no nosso país como leucena, é uma planta difundida por todo o mundo e utilizada como forrageira por apresentar vários nutrientes; no entanto, seu uso é limitado, uma vez que possui uma fitotoxina cuja natureza química é de um aminoácido não proteico denominado de mimosina. Em ruminantes, principalmente em bovinos, esta substância causa efeitos tóxicos como alopecia, anorexia, redução no ganho de peso ou perda de peso, salivação excessiva, lesões esofágicas, aumento da tireoide e queda nas concentrações de hormônios tireoidianos. Em monogástricos também tem sido descrita toxicidade evidenciada por alterações como alopecia e diminuição do ganho de peso; porém, os efeitos sobre estes animais ainda não foram bem estudados. Assim, nesta pesquisa objetivou-se inicialmente desenvolver procedimentos químicos para a extração de mimosina das sementes da L.leucocephala e, a partir disto, realizar estudos biológicos, em ratos, para avaliar a toxicidade geral desse aminoácido bem como seus efeitos nos sistemas imune, endócrino e reprodutor. Na extração da mimosina, obteve-se o rendimento de 2,3%. Realizou-se a administração da fitotoxina, por via oral, a ratos Wistar adultos, nas doses de 25, 40 e 60mg/Kg p.v./dia, durante um período de 28 dias. Foram avaliados os seguintes parâmetros: ganho de peso, consumo de ração, bioquímica sérica, histopatologia (fígado, rins, tireoide, timo e baço), peso relativo de órgãos (rins, fígado, timo, baço e testículos), imunidade celular por meio da atividade de macrófagos intraperitoneais, imunidade humoral por meio do título de anticorpos anti-SRBC e \"plaque forming cell\", dosagem de hormônios séricos (testosterona, corticosterona, T3 e T4) e comportamento sexual. Os dados obtidos no presente estudo revelaram que, embora não fossem detectadas alterações clínicas que indicassem toxicidade, e/ou diminuição no consumo de ração e do ganho de peso, nos animais expostos às diferentes doses de mimosina, estes apresentaram lesões consistentes na tireoide. Além disto, observou-se diminuição da testosterona sérica dos ratos que receberam 60mg/Kg de mimosina. Ainda, nas doses de 40 e 60mg/Kg, verificou-se, por meio da avaliação do comportamento sexual, a diminuição no número de montas, bem como o aumento do intervalo entre elas; e nestas maiores doses os ratos também apresentaram aumento da intensidade de fagocitose de macrófagos intraperitoneais. Portanto, os estudos aqui realizados permitem sugerir que a mimosina, nas baixas doses aqui empregadas, não possui efeitos imunotóxicos; porém apresenta potencial bociogênico em ratos e provavelmente atua como desregulador endócrino. / Leucaena leucocephala is a worldwide plant used as forage; however its use in animal production has been limited since it has a phytotoxin denominated mimosine. It is known that this substance cause toxicity as alopecia, anorexia, reduced weight gain or weight loss, excessive salivation, esophageal lesions, thyroid enlargement and low thyroid hormones in ruminants, mainly in bovines. On the other hand, toxic effects of mimosine have not well studied in monogastric, but alopecia and low weight gain already was also reported. Thus, this study aimed to evaluate in rats the general toxicity of this amino acid as well as its effects on immune, endocrine and reproductive systems. In the first step of the study, it was extracted from seeds of L.leucocephala 2.3% of mimosine that was administrated orally to adult Wistar rats at different doses of 25, 40 and 60mg/kg body weight/ day, for 28 days. It was evaluated the following parameters: weight gain, feed intake, serum enzymes, histopathology (liver, kidney, thyroid, thymus and spleen), relative organs weight (kidney, liver, thymus, spleen and testicles), cellular and humoral immunity, serum hormones (testosterone, corticosterone, T3 and T4) and sexual behavior. No clinical sings of toxicity was observed in animals, but histopathology reveled consistent lesions in the thyroids. Additionally, rats that received 60mg/kg of mimosine presented low serum levels of testosterone, and in rats treated with both doses of mimosine, 40 and 60mg/Kg, it was verified increase in phagocytosis intensity of intraperitoneal macrophages, decrease mounts number and increase in mounts interval. Therefore, our study permits to suggest that although low doses of mimosine does not have immunotoxic effects in rats, it has goitrogenic potential and probably acts as an endocrine disrupter.

A Leucaena leucocephala, popularmente conhecida no nosso país como leucena, é uma planta difundida por todo o mundo e utilizada como forrageira por apresentar vários nutrientes; no entanto, seu uso é limitado, uma vez que possui uma fitotoxina cuja natureza química é de um aminoácido não proteico denominado de mimosina. Em ruminantes, principalmente em bovinos, esta substância causa efeitos tóxicos como alopecia, anorexia, redução no ganho de peso ou perda de peso, salivação excessiva, lesões esofágicas, aumento da tireoide e queda nas concentrações de hormônios tireoidianos. Em monogástricos também tem sido descrita toxicidade evidenciada por alterações como alopecia e diminuição do ganho de peso; porém, os efeitos sobre estes animais ainda não foram bem estudados. Assim, nesta pesquisa objetivou-se inicialmente desenvolver procedimentos químicos para a extração de mimosina das sementes da L.leucocephala e, a partir disto, realizar estudos biológicos, em ratos, para avaliar a toxicidade geral desse aminoácido bem como seus efeitos nos sistemas imune, endócrino e reprodutor. Na extração da mimosina, obteve-se o rendimento de 2,3%. Realizou-se a administração da fitotoxina, por via oral, a ratos Wistar adultos, nas doses de 25, 40 e 60mg/Kg p.v./dia, durante um período de 28 dias. Foram avaliados os seguintes parâmetros: ganho de peso, consumo de ração, bioquímica sérica, histopatologia (fígado, rins, tireoide, timo e baço), peso relativo de órgãos (rins, fígado, timo, baço e testículos), imunidade celular por meio da atividade de macrófagos intraperitoneais, imunidade humoral por meio do título de anticorpos anti-SRBC e \"plaque forming cell\", dosagem de hormônios séricos (testosterona, corticosterona, T3 e T4) e comportamento sexual. Os dados obtidos no presente estudo revelaram que, embora não fossem detectadas alterações clínicas que indicassem toxicidade, e/ou diminuição no consumo de ração e do ganho de peso, nos animais expostos às diferentes doses de mimosina, estes apresentaram lesões consistentes na tireoide. Além disto, observou-se diminuição da testosterona sérica dos ratos que receberam 60mg/Kg de mimosina. Ainda, nas doses de 40 e 60mg/Kg, verificou-se, por meio da avaliação do comportamento sexual, a diminuição no número de montas, bem como o aumento do intervalo entre elas; e nestas maiores doses os ratos também apresentaram aumento da intensidade de fagocitose de macrófagos intraperitoneais. Portanto, os estudos aqui realizados permitem sugerir que a mimosina, nas baixas doses aqui empregadas, não possui efeitos imunotóxicos; porém apresenta potencial bociogênico em ratos e provavelmente atua como desregulador endócrino. / Leucaena leucocephala is a worldwide plant used as forage; however its use in animal production has been limited since it has a phytotoxin denominated mimosine. It is known that this substance cause toxicity as alopecia, anorexia, reduced weight gain or weight loss, excessive salivation, esophageal lesions, thyroid enlargement and low thyroid hormones in ruminants, mainly in bovines. On the other hand, toxic effects of mimosine have not well studied in monogastric, but alopecia and low weight gain already was also reported. Thus, this study aimed to evaluate in rats the general toxicity of this amino acid as well as its effects on immune, endocrine and reproductive systems. In the first step of the study, it was extracted from seeds of L.leucocephala 2.3% of mimosine that was administrated orally to adult Wistar rats at different doses of 25, 40 and 60mg/kg body weight/ day, for 28 days. It was evaluated the following parameters: weight gain, feed intake, serum enzymes, histopathology (liver, kidney, thyroid, thymus and spleen), relative organs weight (kidney, liver, thymus, spleen and testicles), cellular and humoral immunity, serum hormones (testosterone, corticosterone, T3 and T4) and sexual behavior. No clinical sings of toxicity was observed in animals, but histopathology reveled consistent lesions in the thyroids. Additionally, rats that received 60mg/kg of mimosine presented low serum levels of testosterone, and in rats treated with both doses of mimosine, 40 and 60mg/Kg, it was verified increase in phagocytosis intensity of intraperitoneal macrophages, decrease mounts number and increase in mounts interval. Therefore, our study permits to suggest that although low doses of mimosine does not have immunotoxic effects in rats, it has goitrogenic potential and probably acts as an endocrine disrupter.

This study was undertaken to determine the effects and nutritive value of Leucaena leucocephala when it was incorporated in a total mixed ration (TMR) fed to milk goats. This was to test the use of Leucaena to substitute for oilseed cake meals (OSCM) which are believed to be expensive and generally unavailable in many parts of the rural areas of South Africa. Four trials were conducted at the University of Pretoria Research Farm and analyses were carried out at the Nutrition laboratory of the University of Pretoria. Leucaena forage contained enough nutrients to allow it to be used as a substitute for OSCM and to a large extent was also the source of protein and roughage in the TMR. The leaves of Leucaena had a higher crude protein, mineral and mimosine concentration but lower fibre content than the pods and twigs; while the air dried Leucaena forage had a higher crude protein and lower fibre content than sun dried forage. This study showed that there was a higher crude protein and mimosine concentration but a lower fibre concentration from the Leucaena harvested in summer than that harvested in autumn. Milk yield and quality was not adversely affected by the inclusion of Leucaena in the milk goat diet at the rate of 25% of the DM, with the exception of milk urea nitrogen. The inclusion of Leucaena decreased the milk urea nitrogen as compared to that shown from TMR without Leucaena. The body weight and body condition of lactating goats were also not affected by inclusion of Leucaena during the three phases of the lactation period. Therefore, the inclusion of Leucaena in the milk goat diet has been shown to support production of milk in terms of yield and quality which was similar to that of goats fed a commercial diet. There was no significant difference in milk composition in terms of milk lactose and milk protein for milk produced in the morning and afternoon between goats fed the two diets, even though the morning milk yield was higher than the afternoon yield because of the unequal milking intervals. However, the milk composition in terms of milk urea nitrogen, milk fat and somatic cell counts varied greatly between morning and afternoon milking. The apparent digestibility, average daily gain and feed conversion ratio of Saanen male goats were not affected by the inclusion of Leucaena in the TMR, as compared to the TMR without Leucaena. However the voluntary dry matter and nutrients intake were improved by the inclusion of Leucaena in the TMR. No toxicity of mimosine was observed during this study. The results of this study also showed that the inclusion of Leucaena in the total mixed ration had no effect on the carcass characteristics and meat quality of goats as compared to those fed a TMR containing OSCM. / Dissertation (MSc(Agric))--University of Pretoria, 2011. / Animal and Wildlife Sciences / unrestricted

No description available.

Zahlreiche Studien belegen, dass Maillard-Reaktionsprodukte (MRP) in vivo einen Einfluss auf den physiologischen Metallionenhaushalt haben können. Da bisher noch keine Korrelation zwischen dem Entstehen von definierten MRP und einem erhöhten Metallionenbindungsvermögen ermittelt werden konnte, war es das Ziel dieser Arbeit, die Komplexbildungseigenschaften der ausgewählten MRP Nε-Carboxymethyllysin, Isomaltol und Maltosin sowie deren Strukturanaloga Maltol, Deferipron, Mimosin und Pyridosin mit den physiologisch relevanten Metallionen Cu(II), Zn(II), Fe(III), Al(III) und Mn(II) zu untersuchen. Dazu wurden die MRP Nε-Carboxymethyllysin und Maltosin sowie die parallel untersuchten Substanzen Pyridosin, Maltosin-3-benzylether, Nα-Hippuryl- und Nα-Acetylmaltosin in ausreichender Menge und Reinheit synthetisiert. Dabei gelang es, für Maltosin und Pyridosin neue und effiziente Synthesewege zu entwickeln, bei welchen zum ersten Mal beide Substanzen gezielt aufgebaut wurden. Die Komplexbildungskonstanten der Liganden mit den Metallionen wurden pH-potentiometrisch bestimmt (I[KNO3] = 0,15 M; θ = 25 °C). Durch die Auswertung der Protonierungskonstanten der gebildeten Komplexe und das Vermessen geeigneter Derivate konnten für die untersuchten Komplexe zusätzlich die Koordinationsstellen der Liganden aufgeklärt werden. Die Untersuchungen zu den Komplexbildungseigenschaften bestätigten erstmals die Vermutung, dass MRP in der Lage sind, Metallionen zu binden. Dabei wurde weiterhin ermittelt, dass die Bindung von Cu(II) durch Nε-Carboxymethyllysin und von Fe(III), Al(III) und Cu(II) durch Maltosin durchaus von physiologischer Relevanz sind. Die Bedeutung der Ergebnisse wurde qualitativ durch Versuche mit Maltosin-derivatisiertem Rinderserumalbumin unterstrichen. Als besonderes Ergebnis der Arbeit ist herauszustellen, dass das MRP Maltosin und die Verbindung Pyridosin deutlich stabilere Komplexe mit Fe(III) bilden als das zur Fe(III)-Chelattherapie eingesetzte Medikament Deferipron. Diese festgestellte Eigenschaft bietet interessante Perspektiven für zukünftige Studien zur möglichen Anwendung von z. B. Maltosin als Pharmakon. / Several studies show that Maillard reaction products (MRP) may influence the physiological metal ion balance. But none of these studies prove a correlation between the formation of defined MRP and an enhanced metal ion binding. Therefore it was the aim of this work to investigate the complex formation characteristics of the selected MRP Nε-carboxymethyllysine, isomaltol and maltosine as well as the structural analogues maltol, deferiprone, mimosine and pyridosine with the physiological relevant metal ions Cu(II), Zn(II), Fe(III), Al(III) and Mn(II). For that purpose the MRP Nε-carboxymethyllysine and maltosine plus the parallel analysed substances pyridosine, maltosine-3-benzylether, Nα-hippuryl- and Nα-acetylmaltosine were synthesised. Thereby new and efficient syntheses for maltosine and pyridosine were developed. The stability constants of the ligands with the metal ions were determined by pH-potentiometry (I(KNO3) = 0,15 M; θ = 25 °C). Furthermore the donor atoms within the formed complexes were determined by the evaluation of the protonation constants of the formed complexes and by the analysis of adequate derivatives. The studies to the complex formation characteristics confirm for the first time the assumption, that MRP are able to form stable complexes with metal ions. Withal it was ascertained that the coordination of Cu(II) by Nε-carboxymethyllysine and of Fe(III), Al(III) and Cu(II) by maltosine may be of physiological relevance. The significance of the results was pointed out by experiments with maltosine derivatised bovine serum albumine. The fact that the MRP maltosine and the compound pyridosine form more stable complexes with Fe(III) as the medicament for the Fe(III) chelate therapy deferiprone is a particular result of this work. This property affords interesting perspectives for future studies about a possible appliance of e.g. maltosine as pharmaceutical.