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Silva, Lidércia Cavalcanti Ribeiro Cerqueira e. "Desenvolvimento de estratégias analíticas para determinação de flavanonas e psoraleno por CLAE-DAD em sucos de laranjas de diferentes procedências." reponame:Repositório Institucional da UFBA, 2009. http://www.repositorio.ufba.br/ri/handle/ri/9877.
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CAPES
Este trabalho foi desenvolvido no âmbito do PRONEX – NQA e descreve o estudo através da técnica da Cromatografia Líquida de Alta Eficiência acoplada a detector de arranjo de diodos - CLAE-DAD nas análises de amostras de sucos de laranja obtidos por processos extrativos diversificados (espremidos a mão, extração em condições industriais com posterior comercialização em longo prazo e obtido através de máquinas tipo fresh-in-squeeze) para a identificação de flavonóides e psoraleno. Os diversos sucos foram submetidos às etapas de extração líquido-líquido e posterior análises por CLAE-DAD. Estes procedimentos permitiram identificar e quantificar algumas flavanonas e psoraleno presentes nos sucos cítricos. Dentre as flavanonas se determinou hesperidina, naringina, naringenina e poncirina. As faixas de concentrações destes compostos variaram de 17,8 - 245 mg 100 g-1 para hesperidina, 0,01 – 0,08 mg 100 g-1 para naringina, 0,05 – 0,170 mg 100 g-1 para naringenina e de 0,06 – 0,36 mg 100 g-1 para poncirina. Quanto ao psoraleno, em algumas amostras dos sucos, as concentrações estavam abaixo do limite de quantificação (< 0,02) e variou de < 0,02 – 0,05 mg 100 g-1. Estes resultados sugerem que o modo de obtenção dos sucos e os critérios de extração dos constituintes podem influenciar tanto nos teores dos flavonóides no suco como nas detecções de suas concentrações através da técnica aplicada. Para exames das informações geradas foram empregadas metodologias estatísticas multivariadas por meio de Análises de Componentes Principais (PCA) e Análise de Agrupamentos Hierárquicos (HCA) executando o estudo exploratório dos dados para avaliar tendências e discriminar amostras dos sucos de laranja quanto a sua origem, tipos de tratamentos de extração e características químicas para os teores de flavonóides e psoraleno.
Salvador
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Miranda, Amanda Rodrigues. "Estudo da eficácia, segurança e tolerabilidade do Brosimum gaudichaudii Trécul em indivíduos adultos portadores de vitiligo." Universidade Federal de Goiás, 2014. http://repositorio.bc.ufg.br/tede/handle/tede/6126.
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Vitiligo is a chronic disease of skin, acquired and idiopathic, characterized by circumscribed depigmented macules or patches. The treatment is still a challenge and don´t have an effective treatment that may improve all patients. The traditional psoralen photosensitizers are options for the treatment of vitiligo. In the Brazilian cerrado is popularly known action of Brosimum gaudichaudii Trécul (BGT), or mamacadela, which is an herbal psoralen. The goal of this study was evaluate the efficacy, safety and tolerability of BGT in adult patients with vitiligo, in topical and systemic presentations. A randomized controlled trial, double-blind and placebo-controlled was conducted. Of the 58 selected patients, 33 were randomized, 17 in the treatment group (G1) and 16 in the placebo group (G2). These remained until the end of the study 10 patients in G1 and G2 in 6 patients. The interventions were 800 mg / day of medication per orally and use of the ointment for 22 weeks, together with graded and daily photoexposure. The effectiveness of the BGT was assessed using the Vitiligo Area Score Index (VASI), applied by a dermatologist at all clinic visits. Already the safety and tolerability were assessed by laboratory tests before and during treatment, and observation of adverse events. All patients were classified with generalized vitiligo. The group that received the medication (G1) improved significantly VASI in intra-group evaluation (p <0.05) and also a higher proportion of repigmentation compared to G2. The VASI don´t have association with the analysis variables (gender, age, skin type, previous treatment, education, emotional stress, time of diagnosis, treatment adherence) (p> 0.05). Adherence to photoexposure was irregular in both groups, and don´t have statistically significant relationship with changes of VASI (p > 0.05). Laboratory tests showed no significant changes. Adverse events were mild and transient and the most common being erythema, and occurred predominantly in G1 patients. Therefore, it can be concluded that the BGT is effective in the treatment of vitiligo, with safe and well tolerated in the long term.
O vitiligo é dermatose crônica adquirida, idiopática, que se manifesta por manchas acrômicas e bem delimitadas. Seu tratamento ainda é um desafio e não existe até o momento intervenção completamente eficaz. Os psoralenos são fotossensibilizantes tradicionais utilizados para o tratamento do vitiligo. No cerrado brasileiro é popularmente conhecida a ação da planta mamacadela (Brosimum gaudichaudii Trécul (BGT)) devido a presença de derivados psoralênicos em sua composição . O presente estudo teve como objetivo avaliar a eficácia, segurança e tolerabilidade de formulações farmacêuticas contendo extrato de raízes de BGT em pacientes adultos portadores de vitiligo, nas apresentações tópica e sistêmica. Foi realizado ensaio clínico randomizado, duplo-cego e placebo-controlado. Dos 58 pacientes selecionados, 33 foram randomizados, sendo 17 no grupo 1 (G1), de tratamento, e 16 no grupo 2 (G2), placebo. Destes, permaneceram até o final do estudo 10 pacientes no G1 e 6 pacientes no G2. Foram administrados 800 mg/dia da medicação, via oral, além da pomada, durante 22 semanas, associados a fotoexposição diária e gradativa. A eficácia do BGT foi avaliada através do Vitiligo Area Score Index (VASI), aplicado por dermatologista em todas as visitas clínicas. Já a segurança e tolerabilidade foram avaliadas pela realização de exames laboratoriais, antes e durante o tratamento, além da observação de eventos adversos. Todos os pacientes foram classificados com vitiligo generalizado. O grupo que recebeu a medicação (G1) apresentou melhora significativa do VASI na avaliação intragrupos (p<0,05) e também maior proporção de repigmentação quando comparado ao G2. O VASI não demonstrou associação com as variáveis de análise (sexo, idade, fototipo, tratamento prévio, escolaridade, estresse emocional, tempo de diagnóstico, adesão ao tratamento) (p>0,05). A adesão à fotoexposição foi irregular em ambos os grupos e não apresentou relação estatisticamente significante com as alterações do VASI (p>0,05). Em consonância, os exames laboratoriais não apresentaram alterações significativas. Os eventos adversos foram leves e transitórios, sendo mais comum o eritema, e ocorreram predominantemente nos pacientes do G1. Portanto, pode-se concluir que o BGT é eficaz no tratamento do vitiligo, sendo seguro e bem tolerado a longo prazo.
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Nguyen, Christophe. "Contribution à l'étude de la production de psoralène (furocoumarine) par la culture in vitro de plantes du genre psoralea (leguminosae)." Vandoeuvre-les-Nancy, INPL, 1992. http://www.theses.fr/1992INPL085N.
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Nous avons étudié la possibilité d'utiliser la culture in vitro de plantes du genre psoralea pour produire du psoralène une molécule photosensibilisante aux nombreuses applications industrielles. Nous avons tout d'abord envisagé la production de ces composés par la culture en milieu liquide de cellules de p. Cinerea. Nous avons constitue un souchier de 131 cals. La variabilité génétique induite par la mise en culture in vitro a été stabilisée pour la moitie d'entre eux. A partir de ces cals, nous avons également initié des cultures de cellules en milieu liquide les suspensions cellulaires. Nous avons mis en évidence que certains cals et suspensions cellulaires synthétisaient une molécule dont le spectre UV était très voisin de celui du psoralene. L'identité de ce compose demande à être confirmée. Nous avons également aborde la production de psoralène par des racines transformées par agrobacterium rhizogenes. Une souche a été inoculée à sept espèces de psoralées pour constituer un souchier de racines transformées. Cependant, nous n'avons jamais pu détecter de psoralène dans les racines transformées alors que des racines prélevées sur les plantes entières en contiennent
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Silva, Filho Omar Paulino. "Obtenção de pellets a partir dos extratos líquidos padronizados de Brosimum gaudichaudii Trécul (Moraceae) ou Lafoensia pacari A. St.-Hil. (Lythraceae)." Universidade Federal de Goiás, 2014. http://repositorio.bc.ufg.br/tede/handle/tede/7463.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Pellets are spherical solid oral dosage forms that can be used in the development of new pharmaceutical products with standardized plant extracts. Brosimum gaudichaudii Trécul (Moraceae) and Lafoensia pacari A. St.-Hil. (Lythraceae) are typical species from the Cerrado biome. The extract obtained from the roots of B. gaudichaudii is traditionally used in the treatment of vitiligo, its effectiveness is due to the presence of the chemical markers psoralen and bergapten. As for L. pacari, the barks of the branches and trunk are traditionally used in the treatment of gastric ulcers, highly valued for there anti-inflammatory and wound healing because of there ellagic acid content. For each of these species optimal extractive methods exist to obtain standardized liquid extracts. However there are no studies that propose the development of solid oral dosage forms from them. Thus, the present study is aimed at obtaining pellets from the standardized liquid extract of the B. gaudichaudii roots, furthermore to determine the efficiency of a photoprotector coating on the stability of psoralen and bergapten and also obtaining pellets with standardized liquid extract of the L. pacari barks from the branches and trunk. The B. gaudichaudii roots were collected in the city of Jussara, Goiás, and the L. pacari barks in Niquelândia, Goiás. Separately, the raw materials were cleaned, dried in an oven with forced air circulation, then subsequently milled for the extractive process. After the standard liquid extract of B. gaudichaudii had been obtained, six formulas were developed at bench scale. Among these, one stood out by the homogeneity of the lot and the sphericity of its pellets. This formula had been selected to be sacaled-up and it`s composition had been formed by 49.5% (w/w) of microcrystalline cellulose (MCC), 1% (w/w) of hydroxypropylmethyl cellulose (HPMC) and 49.5% (w/w) of that extract. The pellets obtained from the scaled formula were divided into two portions, one of them had been coated with a photoprotective layer and both were subjected to a photostability test. The degradation of the markers had been evident only in the uncoated pellets. The reduction of 1.87% (w/w) in the content of psoralen and 8.1% (w/w) in bergapten content had been observed after 3 J/cm2 exposure to UVB radiation. After exposing to 30 J/cm2 of UVA, there had been a reduction of 24.1% (w/w) of psoralen and 28.48% (w/w) of bergapten. Therefore, the application of the photoprotective coating had been an effective alternative and ensured the stability of the chemical markers after the test. With respect to the liquid extract of L. pacari, 13 formulas were obtained among which only two formed pellets whose batch homogeneity had been greater than 70%. Among them, only one had been chosen to obtain the first scaled-up model. With the production of the scaled-up batch, it had been observed that formulas prepared with a lower proportion of standardized liquid extract of L. pacari had enabled us to obtaing more homogeneous, spherical and a smoother pellets. Based on these results and due to the innovative character of the studies, this work can be used as a model for future trials designed to obtain pellets with standardized liquid extract of B. gaudichaudii or L. pacari.
Pellets são formas farmacêuticas sólidas orais esféricas que podem ser utilizadas no desenvolvimento de novos produtos farmacêuticos a partir de extratos vegetais padronizados. Brosimum gaudichaudii Trécul (Moraceae) e Lafoensia pacari A. St.-Hil. (Lythraceae) são espécies típicas do bioma Cerrado. O extrato obtido das raízes de B. gaudichaudii é utilizado tradicionalmente no tratamento de vitiligo, cuja eficácia se deve pela presença dos marcadores químicos psoraleno e bergapteno. Quanto à espécie L. pacari, são tradicionalmente utilizados as cascas dos galhos e do tronco no tratamento de úlceras gástricas, cuja ação anti-inflamatória e cicatrizante é atribuída ao ácido elágico. Para cada uma destas espécies existem métodos extrativos otimizados para obtenção de extratos líquidos padronizados nos respectivos marcadores químicos. No entanto, não há estudos que proponham o desenvolvimento de formas farmacêuticas sólida orais a partir destes. Assim, o presente trabalho teve como objetivo obter pellets a partir do extrato hidroalcoólico das raízes de Brosimum gaudichaudii, padronizado em psoraleno e bergapteno, determinar a eficácia do revestimento fotoprotetor na estabilidade do psoraleno e bergapteno, além de obter pellets com o extrato hidroalcoólico das cascas dos galhos e do tronco de Lafoensia pacari, padronizado em ácido elágico. As raízes de B. gaudichaudii foram coletadas no município de Jussara, Goiás, e as cascas dos galhos e do tronco de L. pacari em Niquelândia, Goiás. Separadamente, as matérias-primas vegetais foram limpas, secas em estufa com circulação forçada de ar, posteriormente trituradas para a obtenção dos respectivos extratos líquidos padronizados. A partir do extrato líquido padronizado de B. gaudichaudii, foram obtidas seis fórmulas em escala de bancada. Dentre estas, uma se destacou pela homogeneidade do lote e pela esfericidade dos pellets. Deste modo, a fórmula que se destacou foi selecionada e escalonada, sua composição é formada pela mistura de XX% (m/m) de celulose microcristalina (CMC), X% (m/m) de hidroxipropilmetilcelulose (HPMC) e 49,5% deste extrato. Os pellets obtidos a partir da fórmula escalonada foram divididos em duas partes, em uma foi aplicado o revestimento fotoprotetor e ambas foram submetidas ao ensaio de fotoestabilidade. Desse modo, a degradação dos marcadores foi evidente apenas nos pellets sem o revestimento, cuja redução de no teor de psoraleno e bergapteno foi igual a 1,87% (m/m) e 8,1% (m/m), após a exposição a 3 J/cm2 de radiação UVB. Após a exposição a 30 J/cm2 de UVA, houve a redução de 24,1% (m/m) de psoraleno e 28,48% (m/m) de bergapteno. Portanto, a aplicação do revestimento fotoprotetor foi uma alternativa eficaz e garantiu a estabilidade dos marcadores químicos após o ensaio. Com relação ao extrato líquido de L. pacari, foram obtidas 13 fórmulas, dentre as quais apenas duas formaram pellets cuja homogeneidade dos lotes foi superior a 70% e apenas uma foi escolhida como modelo para a obtenção do lote piloto. Com a produção do lote piloto foi observado que fórmulas elaboradas com menor proporção do extrato padronizado de L. pacari e a mecanização do processo de mistura dos componentes da fórmula, possibilitam a obtenção de pellets mais esféricos, homogêneos e com superfície menos irregular. Diante dos resultados obtidos e devido ao caráter inovador dos estudos realizados, este trabalho pode ser utilizado como modelo para ensaios futuros destinados a obtenção de pellets com o extrato líquido padronizado de B. gaudichaudii ou L. pacari.
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Sándor, Zoltán. "Mutagenic properties of psoralen-modified triple helix forming oligonucleotides." Lund : Dept. of Medical Microbiology, Malmö General Hospital, Lund University, 1998. http://catalog.hathitrust.org/api/volumes/oclc/39774150.html.
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Krieger, Célia. "Identification moléculaire et caractérisation fonctionnelle d'une nouvelle sous-famille de cytochromes P450, CYP71AZ, impliquée dans la synthèse de furanocoumarines et coumarines chez Pastinaca sativa." Thesis, Université de Lorraine, 2014. http://www.theses.fr/2014LORR0185/document.
Повний текст джерелаАнотація:
Les furanocoumarines (FCs) sont des métabolites secondaires principalement synthétisés chez quatre familles botaniques et dérivent de la voie de biosynthèse des phénylpropanoïdes. Ces phytoalexines interviennent dans les processus de défense de la plante et présentent un fort potentiel thérapeutique. Des travaux réalisés dans les années 1960 sur des cultures cellulaires en parallèle de l’utilisation de précurseurs radiomarqués ont permis de démontrer que de nombreuses enzymes impliquées dans cette voie appartenaient à la famille des cytochromes P450 (P450s). Seules deux d’entre elles avaient pu être identifiées d’un point de vue moléculaire au début de ce travail de thèse. Afin de générer des informations concernant le génome de plantes productrices de FCs, nous avons fait séquencer les ARNm extraits de feuilles de Pastinaca sativa, de Ruta graveolens et de Cullen cinereum. L’analyse in silico de ces trois banques de données a permis d’identifier près de 800 fragments d’ADNc codants pour des P450s. Des travaux antérieurs réalisés au laboratoire et l’analyse comparative des transcriptomes de ces 3 plantes nous ont amenés à nous focaliser sur la sous-famille CYP71AZ au travers d’une étude fine de CYP71AZ3 et CYP71AZ4. La caractérisation fonctionnelle de ces enzymes a été réalisée dans un système d’expression hétérologue eucaryote : Saccharomyces cerevisiae. Les résultats obtenus ont permis de montrer que CYP71AZ4 avait une spécificité de substrat assez large puisqu’elle pouvait métaboliser au moins une FC et 4 coumarines. L’analyse et la comparaison des constantes cinétiques pour chacun de ces substrats indiquent néanmoins que le psoralène est le substrat préférentiel. La caractérisation fonctionnelle de CYP71AZ3 a mis en évidence que cette enzyme pouvait hydroxyler l’esculétine, une coumarine, mais ne jouait aucun rôle dans la synthèse de FCs. Ces travaux mettent en évidence la diversité fonctionnelle au sein d’une même sous-famille enzymatique et permettent d’émettre des hypothèses nouvelles quant à l’apparition de cette voie de biosynthèse chez les Apiacées d’une part, et chez les autres familles botaniques d’autre partFuranocoumarins (FCs) are secondary metabolites mainly synthetized in four botanical families deriving from the phenylpropanoid biosynthetic pathway. These phytoalexins are involved in plant defense mechanisms and present strong therapeutic potential. Early studies in the 1960s based on cell cultures and the use of radiolabeled precursors have shown that many enzymes involved in this pathway belong to the cytochrome P450 family (P450s). Only two of them had been identified from a molecular point of view at the beginning of this thesis. In order to generate information regarding the genome of plants producing FCs, we sequenced the mRNA extracted from leaves of Pastinaca sativa, Ruta graveolens, and Cullen cinereum. In silico analysis of these three libraries identified nearly 800 cDNA fragments encoding for P450s. Previous studies in the laboratory and comparative transcriptome analysis of these three plants have led us to focus on the subfamily CYP71AZ through a detailed study of CYP71AZ3 and CYP71AZ4. Functional characterization of these enzymes was performed in an eukaryote heterologous expression system: Saccharomyces cerevisiae. The results showed that CYP71AZ4 had a broad substrate specificity enough as it could metabolize one FC and 4 coumarins. The analysis and comparison of the kinetic constants for each of these substrates indicate, however, that the preferred substrate is psoralen. The functional characterization of CYP71AZ3 showed that this enzyme could hydroxylate esculetin, a coumarin, but played no role in the synthesis of FCs. This study highlights the functional diversity within a single enzyme subfamily and allows to issue new hypotheses about the emergence of this biosynthetic pathway in Apiaceae on one hand, and among other botanical families on the other hand
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Doerper, Sébastien. "Modification de la synthèse des furocoumarines chez Ruta graveolens L. par une approche de génie métabolique." Thesis, Vandoeuvre-les-Nancy, INPL, 2008. http://www.theses.fr/2008INPL070N/document.
Повний текст джерелаАнотація:
La rue officinale (Ruta graveolens L) est une plante connue comme étant particulièrement riche en métabolites secondaires et produisant notamment des molécules d’intérêt pharmaceutique comme les furocoumarines. Nous avons tenté par une approche de génie métabolique d’augmenter la teneur en furocoumarines produites dans les plantes. La mise en place de telles approches nous a également permis de mieux comprendre les mécanismes de régulation de la voie de biosynthèse des phénylpropanoïdes. Pour atteindre ces objectifs nous avons transformé la rue avec différents gènes placés sous le contrôle d’un promoteur constitutif fort, le promoteur 35S du CaMV. Pour chaque série de transformants nous avons étudié la teneur en furocoumarines et analysé les variations de composés phénylpropanoïdes (rutine, umbelliférone, ferulate, scopolétine). Parallèlement à cette analyse métabolique, une corrélation a été réalisée avec le niveau d’expression des transgènes et de certains endogènes par l’utilisation d’approche de PCR quantitative. Les séries de plantes transgéniques surexprimant les gènes codants pour la Coumaroyl ester 3’-Hydroxylase de rue (CYP98A22) et d’A. thaliana (CYP98A3) présentent toutes les deux une augmentation significative d’une facteur 3 de la teneur en furocoumarines. Par contre si les premières sont caractérisées par une diminution de la production en rutine et en umbelliférone, les secondes présentent une augmentation importante de la teneur en Scopolétine et en umbelliférone. Ces résultats suggèrent la coexistence de deux C3’H chez R. graveolens ayant des fonctions différentes, l’une d’entre elles étant impliquée directement ou non dans la synthèse de scopolétine. Si la transformation génétique de rues avec des gènes de la famille CYP98A induit des modifications du métabolisme secondaire, la surexpression d’un gène spécifique à la voie de biosynthèse des furocoumarines (gène cyp71AJ1, codant pour la psoralène synthase d’A. majus) permet d’augmenter uniquement la teneur en furocoumarines (X4). L’ensemble de ces travaux a permis de montrer l’intérêt d’une approche de génie métabolique pour générer des plantes présentant un intérêt potentiel pour la production de molécules d’intérêts pharmaceutiquesGarden Rue (Ruta graveolens L.) is a plant known as being particularly rich in secondary metabolites and in particular producing molecules of pharmaceutical interest like furocoumarines. By the use of a metabolic engineering approach, we tried to increase the content of furocoumarines produced in these plants but also to better understand the regulation mechanisms of the phenylpropanoïd biosynthesis pathway. To achieve these goals we transformed Ruta plants with various genes placed under the control of a strong constitutive promoter, CaMV 35S promoter. The plants we obtained were analyzed for their ability to overproduce furocoumarines but also other phenylpropanoïds like ferulate, umbelliferone, scopoletine or rutin. Using Real Time PCR experiments, a correlation was carried out with the level of expression of each transgene and several endogenous genes. Plants overexpressing either the Ruta or the Arabidopsis Coumaroyl ester 3 '-Hydroxylase (CYP98A22 and CYP98A3 respectively) display both a significant increase (3 time level) of the furocoumarin. However if the S-98A22 plants are characterized by a reduction in the production of rutin and umbelliferone, S-98A3 transgenic plants display a significant increase scopoletine and umbelliferone content. These results suggest the coexistence of two C3'H having different functions in Ruta. One of them might be involved more specifically in the synthesis of scopoletine. If the transformation of Ruta with genes belonging to the CYP98A family generates an enlarged of the secondary metabolism, we also showed that the overexpression of a gene belonging to the furocoumarins biosynthesis pathway (CYP71AJ1, the psoralen synthase) allowed a specific stimulation. Indeed a 4 time increase of the content of furocouramins was noticed in these transgenic plant lines. This work made it possible to make evidence of the interest of a metabolic engineering approach to generate plants of interest for the production of pharmaceutical molecules
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Reis, Karinna Bannach. "Extrato padronizado de Ruta graveolens L.: avaliação de seu potencial no controle da brusone em arroz." Universidade Federal de Goiás, 2013. http://repositorio.bc.ufg.br/tede/handle/tede/3066.
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Ruta graveolens has been successfully applied for many human diseases treatment and promises a well succeed alternative for plant diseases control because it has also phytoalexins in its composition. The aim of this study was to standardise the R. graveolens liquid extract and evaluate its potential for controlling rice (Oryza sativa) leaf blast (Magnaporthe oryzae). The drug has been characterized, the liquid extract obtained and the methodology for quantifying the standards components, furanocoumarins psoralen and bergapten, validated by high performance liquide chromatography. The components of essential oil obtained from standardized liquid extract were characterized by gas chromatography-mass spectrometry. In a completely randomized design, conducted in artificial hydrophobic surface with three replications and eleven treatments composed of M. oryzae conidial suspension (105 con.ml-1) mixed with R. graveolens standardized extract (0.01 to 0.10 g.mL-1), or furocoumarins psoralen (0.18 to 1.82 μg. mL-1), or bergapten (0.29 to 2.91 μg. mL-1), or water (control). It was evaluated the inhibition of conidial germination and appressorium formation and the median lethal dose (LD50). A second assay, in a completely randomized design in three replications was conducted in greenhouse conditions. It was composed of 21 days old rice plants, which were sprayed with a mixture containing M. oryzae conidial suspension (3x105 con.ml-1) and R. graveolens extract, without dilution, or furocoumarins psoralen (18.26 μg. mL-1), or bergapten (29.14 μg. mL-1), or water (control). Nine days after inoculation, leaf blast severity was scored with a diagrammatic scale, the data were statistically analyzed and means compared. The standardized plant extract inhibited M. oryzae conidial germination (LD50=0.237mg) and appressorium formation (LD50=0.121 mg) up to 100% and reduced 80.84% of leaf blast. By fluorescence microscopy it was possible to observe that standardized plant extract did not damage M. oryzae cell wall and plasma membrane, indicating another type of interaction to inhibit conidia development. Isolated standards furanocoumarins psoralen and bergapten did not inhibit conidial germination and appressorium formation and reduce leaf blast severity proportionally, suggesting that synergistic interactions between extract and essential oil components were responsible for the success of R. graveolens in suppressing rice disease, making it an alternative to compose rice blast management.
Ruta graveolens é utilizada com sucesso no tratamento de diversas patologias humanas e possui potencial para o controle alternativo de fitopatógenos, pois também apresenta fitoalexinas em sua composição. O objetivo deste estudo foi padronizar o extrato vegetal líquido de R. graveolens e avaliar seu potencial para o controle da brusone foliar. O material vegetal foi caracterizado, o extrato líquido obtido e a metodologia para a quantificação dos padrões psoraleno e bergapteno foi validada por cromatografia líquida de alta eficiência. Os componentes do óleo essencial obtidos a partir do extrato líquido padronizado foram caracterizados por cromatografia gasosa acoplada à espectrometria de massas. No ensaio conduzido em superfície hidrofóbica artificial, com três repetições e onze tratamentos, 10 μL da suspensão de conídios de Magnaporthe oryzae (105 con/mL) foram misturadas com o extrato vegetal padronizado (0,01 a 0,10 g/mL), ou as furanocumarinas psoraleno (0,18 a 1,82 μg/mL) e bergapteno (0,29 a 2,91 μg/mL), ou água (controle). Avaliou-se a inibição da germinação conidial e da formação dos apressórios determinando-se a dose letal capaz de inibir 50% dos indivíduos (DL50). No experimento conduzido em casa de vegetação e com três repetições, plantas de arroz com 21 dias após plantio foram pulverizadas com uma suspensão de conídios de M. oryzae (3x105 com/mL) misturada com extrato vegetal padronizado sem diluição, ou psoraleno (18,26 μg/mL), ou bergapteno (29,14 μg/mL), ou água (controle). Após nove dias da inoculação, avaliou-se a severidade de brusone foliar com uma escala de 10 graus, os dados foram analisados estatisticamente e as médias comparadas. O extrato vegetal padronizado inibiu a formação de tubo germinativo (DL50= 0,237 mg) e a formação de apressório (DL50= 0,121 mg) de M. oryzae em até 100%, e reduziu a severidade de brusone nas folhas em 80,84%. Através de microscopia de fluorescência, não foi observada ação do extrato padronizado em membrana plasmática e parede celular de M. oryzae, o que indica outro tipo de interação para inibir o desenvolvimento do conídio. Os padrões psoraleno e bergapteno não inibiram proporcionalmente a germinação e a formação de apressório, como também não reduziram a severidade de brusone nas folhas em sua forma isolada, o que sugere que interações sinérgicas entre os diversos componentes do extrato e do óleo essencial de R. graveolens foram responsáveis pelo sucesso do extrato padronizado em suprimir a brusone foliar, tornando-o uma alternativa para compor o manejo de brusone em arroz.
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Holland, Julie. "Studies on the genetic and biochemical properties of a PUVA hyper-resistant mutant of Escherichia coli." Thesis, Nottingham Trent University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259195.
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BUSSEY, CECILE. "Composes bifonctionnels derives du psoralene : synthese et activite cutanee." Université Louis Pasteur (Strasbourg) (1971-2008), 1992. http://www.theses.fr/1992STR13098.
Повний текст джерелаАнотація:
Nous rapportons la synthese de nouvelles furocoumarines angulaires et lineaires, a partir de furocoumarines naturelles et par construction du systeme tricyclique. Dans un premier chapitre est decrite la preparation d'un compose heterodimerique forme d'une furocoumarine lineaire reliee par une chaine o-alkyle en position 5 a une 3-methylene-2-dihydrofuranone. Dans un deuxieme chapitre, nous decrivons la preparation d'un compose heterodimerique forme d'une furocoumarine angulaire reliee par une chaine alkyle en position 5 a une 3-methylene-2-dihydrofuranone, puis la preparation de furocoumarines lineaires substituees en position 5 par une chaine alkyle. Dans un troisieme chapitre, l'activite des deux composes heterodimeriques sur la peau a ete evaluee en utilisant un modele murin. Ces composes se sont reveles non phototoxiques, et le derive comportant un noyau furocoumarine lineaire a montre au cours d'une experience preliminaire un effet antiproliferatif sur les lymphocytes t
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Robinson, Scott D. "Measurement of 8-Methoxypsoralen concentration using fluorescence." Full text open access at:, 1995. http://content.ohsu.edu/u?/etd,243.
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Sakuntabhai, Anavaj. "Improvement of psoralen photochemotherapy : photobiological, pharmacological and clinical studies." Thesis, University of Newcastle Upon Tyne, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309063.
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Gimenez-Arnau, Elena. "Synthese et activite photobiologique de composes bifonctionnels derives du psoralene." Université Louis Pasteur (Strasbourg) (1971-2008), 1995. http://www.theses.fr/1995STR13160.
Повний текст джерелаАнотація:
En nous interessant a la recherche de nouveaux derives du psoralene, antiproliferatifs mais non-phototoxiques, nous avons synthetise des molecules bifonctionnelles possedant un noyau furocoumarine relie par une chaine polymethylene a une -methylene--butyrolactone. Ces molecules se sont averees non-phototoxiques lorsqu'elles ont ete testees a l'aide d'un modele murin. Nous avons etudie le comportement photodynamique de ces nouveaux derives du psoralene et les nouveaux mecanismes d'interaction possibles entre ce genre de molecules et l'adn. Trois types de molecules modeles pour l'etude de la photo-reactivite intramoleculaire ont permis de verifier que la partie coumarine du psoralene reagit facilement, a 365 nm, avec des doubles liaisons a caractere nucleophile. La double liaison exomethylenique etant particulierement electrophile, une telle reaction entre la lactone et le psoralene des derives -methylene--butyrolactone-psoralene semblait au depart peu favorable. Nous avons constate la formation de produits de cycloaddition intramoleculaire 2+2 entre la double liaison 3,4 du psoralene et la double liaison exocyclique de la lactone. Ces etudes ont permis de constater que les -methylene--butyrolactones sont sensibles a la lumiere uva. Ce type de lactones etant connues comme des accepteurs de michael ou viennent s'additionner les residus nucleophiles des chaines laterales d'acides amines constituant les proteines, une telle photo-reactivite n'avait jamais ete observee. Nous avons demontre ensuite que les -methylene--butyrolactones peuvent reagir photochimiquement avec la thymine. Nous rapportons donc la premiere evidence de la capacite potentielle des -methylene--butyrolactones de former des adduits 2+2 avec l'adn apres irradiation. Enfin, la derniere partie de ce travail est consacree a l'etude du comportement photochimique de ces composes heterodimeriques en presence d'adn ainsi qu'a l'etude de leur action phototoxique, en comparaison avec celle de quelques furocoumarines naturelles
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Cox, George Warren. "8-methoxypsoralen-mediated impairment of human lymphocyte proliferation in vitro in the absence of ultraviolet irradiation : immunological and biochemical mechanisms /." The Ohio State University, 1987. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487324944213995.
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Muret, Patrice. "Contributions pour une meilleure optimisation de la 5-methoxy-psoralene uvatherapie." Besançon, 1993. http://www.theses.fr/1993BESA3711.
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Humbert, Philippe. "Contribution a l'etude pharmacologique des tetracyclines et du 5-methoxypsoralene." Besançon, 1993. http://www.theses.fr/1993BESA3701.
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Decloquement, Laurence. "Cinetiques seriques du 8 methoxypsoralene et chromametrie cutanee : application a la conduite d'une puvatherapie." Lille 2, 1990. http://www.theses.fr/1990LIL2M305.
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Chen, Tongqian. "Synthesis, evaluation and mechanistic studies of halogenated psoralen and acridine phosensitizers /." The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487861796819009.
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Dludlu, Meshack. "Systematic studies of the southern African Psoraleoid legumes." Master's thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/11735.
Повний текст джерелаАнотація:
Includes abstract.Includes bibliographical references (leaves 147-176).
The Psoraleeae are of worldwide distribution, consisting of 185 species in nine genera. More than 60 % of the species are members of the genera, Otholobium C.H.Stirt and Psoralea L., both of which have a centre of diversity in the Cape Floristic Region of South Africa. This dissertation was aimed at conducting a systematic study of the southern African Psoraleeae.
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Kraemer, Cristine Kloeckner. "Determinação da dose fototóxica mínima na terapia com psoraleno e UVA (PUVA)." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2004. http://hdl.handle.net/10183/5435.
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Fersi, Hannan. "Time-resolved spectroscopic studies of Psoralens, Khellin, Visnagin and Lumichrome and derivatives." The Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1141847576.
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Joerges, Christoph. "Einfluss von Psoralen und UVA (PUVA) auf den Zellteilungszyklus von humanen Keratinozyten." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-62273.
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Glenn, L. Lee. "Limited Effectiveness of Psoralen- and Ultraviolet-Inactivated Vaccinia Virus on Shiv Infection." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/7517.
Повний текст джерелаАнотація:
Excerpt: The title and conclusions of the study recently published by Jones et al. (1) concluded that monkeys were protected from dying from a form of simian-human immunodeficiency virus (SHIV) by an psoralen- and ultraviolet-inactivated vaccinia virus in a multi-envelope DNA-VV-protein (DVP). However, the findings in the study are more equivocal than indicated by the title because the effectiveness of the modified vaccinia virus was not decisively demonstrated.
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Giuriato, Nathalie. "Toxicité génétique des psoralènes." Bordeaux 2, 1993. http://www.theses.fr/1993BOR2P007.
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Cole, Jessica Michelle. "The Limitations of DNA Interstrand Cross-link Repair in Escherichia coli." PDXScholar, 2018. https://pdxscholar.library.pdx.edu/open_access_etds/4489.
Повний текст джерелаАнотація:
DNA interstrand cross-links are a form of genomic damage that cause a block to replication and transcription of DNA in cells and cause lethality if unrepaired. Chemical agents that induce cross-links are particularly effective at inactivating rapidly dividing cells and, because of this, have been used to treat hyperproliferative skin disorders such as psoriasis as well as a variety of cancers. However, evidence for the removal of cross-links from DNA as well as resistance to cross-link-based chemotherapy suggests the existence of a cellular repair mechanism. Characterizing the pathways involved in DNA interstrand cross-link repair has been challenging due to the inherent structure of the damage as it precludes the use of an undamaged, complementary strand of DNA as a template for repair.
A number of models of cross-link repair have been proposed based on the identification of hypersensitive repair mutants as well as biochemical evidence that specific repair enzymes are capable of incising cross-linked structures from DNA. Together, these models have suggested the involvement of multiple repair pathways--such as nucleotide exicision repair, translesion synthesis, recombination of double-strand breaks, and base excision repair--operating in sequential steps to correct the damage. Most of the studies from which these models arose are complicated by the fact that cross-linking agents induce multiple forms of damage or they lack in vivo confirmation of how the repair phenomenon occurs in organisms.
In this study, I use Escherichia coli as a model organism to examine the involvement of the aforementioned pathways in DNA interstrand cross-link repair in vivo. This organism was useful in early cross-link studies and, with its highly conserved repair processes, maintains the potential for delineating how cross-links are removed in higher organisms. In Chapter I, I introduce background information on different cross-linking agents, the complications of studying cross-link repair, and the candidate repair pathways that have been implicated to date.
In Chapter II I demonstrate that there is a limited involvement of the nucleotide excision repair helicase, translesion polymerases, and double-strand break repair enzymes through survival analysis of cells defective in these proteins. For this analysis, I use 8-methoxypsoralen plus UVA as a cross-linking agent and angelicin plus UVA as a monofunctional comparator. The observation that uvrD mutants-- defective in helicase II of nucleotide excision repair--were nearly as resistant to 8-methoxypsoralen-induced damage as wild type cells led me to examine the incision rate of cross-links from endogenous plasmid DNA. Surprisingly, cross-links were not efficiently removed from DNA in uvrD mutants relative to wild type cells. These seemingly contradictory results were rectified when I quantified cross-link formation in cell cultures and revealed that as few as one cross-link per chromosome can inactive wild type cells, a lethal quantity that is lower than what has been previously reported. Taken together, these observations suggest that although cross-links are incised in wild type cells, repair is still not a highly productive event in E. coli.
In Chapter III I examine the involvement of the base excision repair pathway in cross-link repair and demonstrate that Nth and Fpg Glycosylases, Xth and Nfo AP-Endonucleases sensitize Escherichia coli to psoralen-induced DNA damage. This is shown by comparative survival analysis in angelicin plus UVA and 8-methoxypsoralen plus UVA treatment whereby nth-, fpg-, and xth-mutants are each more resistant than wild type cells to either treatment. This suggests that when these gene products are present they impact the production or removal of monoadducts. nfo-mutants were different in that the cells were only hyperresistant to 8-methoxypsoralen monoadducts and cross-links, either implying that the Nfo enzyme interacts specifically with psoralen monoadducts rather than angelicin monoadducts or that the enzyme impedes cross-link removal.
Finally, in Chapter IV a summary of the results is provided as well as future directions that may be explored following this study.
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Vare, Daniel. "Interstrand Crosslinks - Induction and repair." Doctoral thesis, Stockholms universitet, Institutionen för genetik, mikrobiologi och toxikologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-78797.
Повний текст джерелаАнотація:
DNA crosslinking agents exhibit a variety of DNA lesions, such as monoadducts, DNA-DNA interstrand or intrastrand crosslinks or DNA-protein crosslinks. Agents that produce interstrand crosslinks (ICLs) exist naturally and are widely used in chemotherapy. Therefore, it is important to understand how the lesions induced by these agents are repaired. In bacteria, the repair is mainly dependent on nucleotide excision repair (NER) together with homologous recombination (HR) or translesion synthesis (TLS). In human cells, it is not clear how these lesions are repaired, and it is believed to be a more complicated process in which NER does not play as important a role as in prokaryotes. Here, we investigated the repair mechanisms mainly after treatment with psoralen but also with acetaldehyde, cisplatin and mitomycin C in some studies. As expected from studies on plasmids and in bacteria, we used new techniques to confirm that various ICL-inducing agents block replication fork elongation in mammalian cells. We also found that the replication fork was unable to bypass these lesions. We confirmed that ERCC1/XPF and the HR proteins BRCA2 and XRCC2/3 are vital for protection against ICL treatments. These proteins were also found to be equally important for the repair of monoadducts. To better understand ICL repair in mammalian cells, we developed a method to study the induction and unhooking of ICL in human fibroblasts. We found that ICLs were repaired and that 50% of the induced ICLs were unhooked within 3 hours following exposure. Additionally, we determined that XPA, but not XPE, is involved in ICL unhooking, although not affecting lethality. A step in ICL repair is the formation of double-strand breaks (DSBs), and we identified a replication-dependent formation of DSBs following ICL treatment. Furthermore, ERCC1/XPF was not necessary for DSB formation. The repair of these DSBs was performed by HR and involved ERCC1/XPF. Additionally, we were able to quantify the ICL unhooking in human fibroblasts and found that they can unhook ~2500 ICL/h. We also determined that a dose of approximately 400 ICL/cell is lethal to 50% of the cells, indicating that ICL unhooking is not the most critical step during the repair process.DNA-skadande ämnen är vanligt i cancerbehandling, då snabbt växande celler, såsom cancerceller är betydligt känsligare än normala celler för DNA skador. En grupp av ämnen som vanligen används i cancerbehandling är korsbindare av DNA. Dessa ämnen kommer reagera två gånger med DNA och skapa två bindningar mitt emot varandra. DNA strängen, som består av två delar, måste kunna separeras och kopieras (replikation) på ett tillförlitligt sätt för att cellerna ska kunna dela sig och bli flera. DNA strängen måste också kunna dela sig och bli avläst rätt för att nya proteiner ska kunna bildas (transkription). När korsbindarna har bundit till DNA strängarna, hindrar detta deras separation och därigenom förhindras även avläsningen och kopieringen. För att göra undersökningarna av DNA korsbindande ämnen ännu lite svårare, så ger korsbindare flera olika typer av skador. Dels kan det bli flera olika typer av korsbindningar, både mellan två DNA-strängar (ICL) vilket är den farligaste och mest svårreparerade typen, men det kan också ske inom samma DNA-sträng (intrastrand crosslink) eller mellan en DNA-sträng och ett protein (DNA-protein crosslink). Korsbindare kan även bilda enbindningsskador (monoaddukt), vilket innebär den bara binder en gång till DNA. För att cellen ska kunna överleva, så måste den reparera skadorna och ta bort korsbindningen eller monoaddukten. Hur detta sker i människor är inte helt klarlagt men det verkar som det sker i flera steg. Till att börja med klipps DNA sönder i ena strängen på båda sidorna om korsbindningen, detta gör att den kvarvarande delen av korsbindningen kan böjas bort. Därefter kommer cellen att skapa nytt DNA för att fylla mellanrummet som bildats. Cellen använder sig av den andra DNA strängen som mall för att sätta in rätt DNA baser, men i fallet med korsbindande ämnen så är även den strängen skadad och därför finns det en stor risk för att fel DNA baser sätts in och då uppstår mutationer. Nästa steg är att klippa den kvarvarande delen av korsbindningen, även denna gång skapas ett mellanrum som måste fyllas med nya baser. Den första artikeln i avhandlingen handlar om att försöka reda ut om det är ICLen eller monoaddukten som är orsak till olika effekter som påträffas efter behandling med korsbindande ämnen. Det vi fann var att även om det bara var från ICLs som vi kunde mäta en effekt på replikationen, så fick vi nästan lika stark effekt från monoaddukterna, som från ICL, för en av de vanligast använda markörerna (kännetecknen) för båda DNA strängarna var brutna på samma ställe (dubbelstränsbrott). Detta berodde dock inte på att även monoaddukterna skapade dubbelsträngsbrott, utan på att markören vi använde var ospecifik. Vi fann även att även om ICLs har mycket större effekt än monoaddukten på cellens överlevnad m.m., så kan man inte bortse ifrån effekten av monoaddukten och att den troligen har en betydande roll för de korsbindande ämnen som endast ger en liten del ICLs. I artikel två har vi utvecklat en ny metod, som gör det möjligt att mäta hur många ICLs som bildas vid en viss dos av de korsbindande ämnen vi undersöker. Vi kan även mäta hur fort ICLerna kan repareras i mänskliga celler med hjälp av metoden. Tack vare en kombination av våra mätningar och med hjälp av datorsimuleringar, kunde vi räkna ut hur många ICLs som bildades per dos för tre vanliga korsbindare. Vi kunde även visa att 50 % av ICLen har påbörjat reparationen och kommit så långt att de var bortklippta från ena stängen inom 3 timmar efter behandlingen. I artikel tre undersöker vi vilka proteiner som är inblandade i den tidiga delen av ICL reparationen, alltså fram till och med att celler klipper ut korsbindningen på båda sidorna om skadan i ena strängen. Här visar vi att celler som är defekta i reparationsprotein kallat XPA, har en betydligt långsammare borttagning av ICLer än vad båda normala celler och celler defekta i reparationsprotein XPE har. Vi visar även att detta inte påverkar cellens replikationshastighet, eller har någon effekt på cellens överlevnad. Den fjärde artikeln handlar om acetaldehyd, som bildas när alkohol förbränns i kroppen. Acetaldehyd har föreslagits bilda ICL och därför undersökte vi vilka effekter den har på cellerna. Vi visar i den här artikeln att det krävs nysyntes av DNA för att acetaldehyd ska leda till dubbelsträngsbrott. Celler kan reparera dessa dubbelsträngsbrott med hjälp av reparationssystem, som kallas homolog rekombination, men att reparationen ibland blir felaktig. I den femte och sista artikeln i avhandligen undersöker vi ett av de vanligast föreslagna proteinen för att sköta klippningen av DNA (ERCC1/XPF) och hur den är inblandad i reparationen av korsbindningar. Vi kan här visa att även det krosbindande ämnet mitomycin C bromsar replikationshastigheter och att ERCC1/XPF är nödvändigt för att kunna fullfölja homolog rekombination av ICLs.
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Submitted. Paper 2: Manuscript. Paper 3: Manuscript. Paper 4: Submitted.
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Costa, Amanda Karla Campos da. "Revalidação de metodo analitico para psoraleno e bergapteno, em HPLC-PDA, aplicado a amostras microdialisadas." Universidade Federal de Goiás, 2014. http://repositorio.bc.ufg.br/tede/handle/tede/4670.
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Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG
Several biological activites...
Diversas atividade biológicas são ...
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Moysan-Le, Meur Annie. "Caracterisation de dosage des produits de photoaddition de psoralene dans l'adn "in vitro" et dans l'adn cellulaire." Paris 6, 1987. http://www.theses.fr/1987PA066021.
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Kobertz, William Rudolf 1968. "Total synthesis of a Furan-side psoralen-thymidine monoadduct and its biochemical applications." Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/50343.
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Kagan, Shashi S. "Synthesis of photoactive psoralen derivatives and evaluation of their potential as antiviral agents /." The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487951595503071.
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Tatchen, Jörg. "Spin-verbotene photophysikalische Prozesse in organischen Molekülen: Entwicklung quantenchemischer Methoden und Anwendung auf Psoralene." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=980417333.
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Limper, Christian [Verfasser]. "Toxische Effekte phenolischer Inhaltsstoffe aus Psoralea corylifolia / Christian Limper." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2014. http://d-nb.info/1046404482/34.
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Rojoa, N. Z. "Re-classification of the tribe Psoraleae using morphological and physiological characters." Bachelor's thesis, University of Cape Town, 2001. http://hdl.handle.net/11427/26645.
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Geenen, Sarah [Verfasser], Thomas J. J. [Gutachter] Müller, and Peter [Gutachter] Gilch. "Synthese und Eigenschaften neuartiger Donor-Akzeptor-Psoralen-Chromophore / Sarah Geenen ; Gutachter: Thomas J.J. Müller, Peter Gilch." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2020. http://d-nb.info/1214439659/34.
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Bello, Abubakar. "Taxonomy and evolutionary studies on the genus Psoralea L. (Psoraleeae, Fabaceae)." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/23460.
Повний текст джерелаАнотація:
Psoraleeae is a tribe of the papilionoid legumes in Fabaceae comprising ca. 223 species in nine genera. Members of Psoraleeae are distributed worldwide, though they mainly occur in the temperate biomes. Of these, ca. 60% of the species (mostly in Otholobium and Psoralea) are endemic to southern Africa predominantly in the Greater Cape Floristic Region (GCFR). The genus Psoralea, consisting of 75 species endemic to southern Africa, is the second most speciose legume in the GCFR after Aspalathus (280 species). This thesis, consisting of a literature review, three research chapters and synthesis, studies the taxonomy, evolutionary history and biogeography of Psoraleeae with an emphasis on Psoralea.
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Rodrigues, Mariana Cristina de Morais. "Desenvolvimento de formas farmacêuticas sólidas contendo extratos padronizados em psoraleno e bergapteno a partir de Brosimum gaudichaudii." Universidade Federal de Goiás, 2016. http://repositorio.bc.ufg.br/tede/handle/tede/5892.
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Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Brosimum gaudichaudii Trécul. from the Moraceae family is traditionally used as a therapeutic resource to treat leukoderma. The roots are the plant’s part that contain the highest concentration of photosensitizing substances, important against leukoderma, among them psoralen and bergapten that belong to the secondary metabolite class named linear furanocoumarins. By definition, phytotherapic is the product obtained exclusively from active vegetal raw material with prophylactic, curative or palliative purpose. They characteristically do not include isolated or highly purified substances in their composition from any source, or are associated with other extracts. One of the main challenges in producing phytotherapic medicine is the complex composition of the medicinal plant that depends on climatic and geographic factors, and cultivation, drying and storage conditions. The objective of this work was to obtain solid pharmaceutical forms containing extract standardized in psoralen and bergapten of B. gaudichaudii, as well as the analyses of these pharmaceutical forms following all the parameters stated by the Normative instruction no 04 of 2014. Chapter 1 is about the vegetal drug characterization and posterior production and standardization of the liquid extract, the analytical method was co-validated by High Efficiency Liquid Chromatography (CLAE) to determine the markers levels in the liquid extract, according to ANVISA norms. The method presented to be selective, linear, precise and exact. The liquid extract was standardized in total furanocoumarins expressed in psoralen and bergapten, and the level was 0.20% (m/v) (20.81 μg/mL of psoralen and bergapten). Chapter 2 describes the development of coated pellets containing the liquid standardized extract, having an average diameter of 0.75±0.08 mm and sphericity of 0.98±0.09. The acquired pellets were encapsulated in hard gelatinous capsules (500 mg of pellets per capsule), the average level of total furanocoumarins per capsule was 641.41 μg. Tablets containing the coated pellets were produced, and it was possible to keep the pellets whole, even after the compression force of 0.5 ton was applied on them. The tablets were tested according to the analyses recommended by the Brazilian Pharmacopeia and presented a total furanocoumarin level of 587.6 μg per tablet. The analytical methodology was co-validated for the quantification of psoralen and bergapten in the coated pellets and the tablets containing them. Chapter 3 describes the obtainment and standardization of the soft extract from B.gaudichaudii and the development of tablets containing the soft extract. The soft extract was characterized according the pharmacopeia tests, and there were 82.02% (m/m) of dry residue, and the total furanocoumarin levels expressed in psoralen and bergapten was 2.93% (m/v) (58.8 μg/g of psoralen and bergapten). Three different formulations of tablets containing soft standardized extract were acquired by humid rout previous granulation. In each formulation the diluents, microcrystalline cellulose (MCC) and starch proportion were variated. The compression was done in a hydraulic press and the process was controlled to establish the compression conditions. The analytical methodology was co-validated to quantify the total furanocoumarins in the tablets and the level were 16,800 μg per tablet.
Brosimum gaudichaudii Trécul. pertencente a família Moraceae é tradicionalmente utilizada como recurso terapêutico para o tratamento de leucodermias .A raiz desta planta é a parte que contém maior concentração de substâncias fotossensibilizantes importantes contra leucodermias, dentre elas o psoraleno e o bergapteno que pertencem à classe de metabólitos secundários denominados furanocumarinas lineares. Por definição, fitoterápico é o produto obtido exclusivamente de matéria prima ativa vegetal com propósito profilático, curativo ou paliativo. Caracterizam-se por não incluir na sua composição substâncias ativas isoladas ou altamente purificadas, de qualquer origem, nem as associações dessas com outros extratos. Um dos principais desafios na produção de um medicamento fitoterápico é a complexidade da composição da planta medicinal, que depende de fatores climátios, geográficos, condições de cultivo, secagem e armazenamento. O presente trabalho teve como objetivo a obtenção de formas farmacêuticas sólidas contendo o extrato padronizado em psoraleno e bergapteno de B. gaudichaudiii, bem como a análise destas formas farmacêuticas seguindo todos os parâmetros exigidos pela Instrução normativa n° 04 de 2014. O capítulo 1 trata da caracterização da droga vegetal e posteriormente a obtenção e padronização do extrato líquido, covalidou-se o método analítico por Cromatografia a Líquido de Alta Eficiência (CLAE) para determinação dos teores dos marcadores no extrato líquido, segundo as normas da ANVISA. O método mostrou-se seletivo, linear, preciso e exato. O extrato líquido foi padronizado em furanocumarinas totais expressas em psoraleno e bergapteno, e obteve-se o teor de 0,20% (m/v) (20,81 μg/mL de psoraleno e bergapteno). O capítulo 2 descreve o desenvolvimento de pellets revestidos contendo o extrato líquido padronizado obtido, tendo um diâmetro médio 0,75+0,08 mm e esfericidade 0,98+0,09. Encapsulou-se os pellets obtidos em cápsulas gelatinosas duras (500mg de pellets por cápsula), o teor médio de furanocumarinas totais por cápsula foi 641,41μg. Obteve-se comprimidos contendo pellets revestidos e foi possível manter os pellets íntegros mesmo após aplicada à força de compressão de 0,5 ton nos mesmos. Os comprimidos foram analisados segundo os testes preconizados pela Farmacopeia Brasileira e apresentaram um teor de furanocumarinas totais de 587,6μg por comprimido. A metodologia analítica foi covalidada para quantificação do psoraleno e bergapteno tanto nos pellets revestidos como nos comprimidos contendo pellets. O capítulo 3 descreve a obtenção e padronização do extrato mole de B.gaudichaudii e o desenvolvimento de comprimidos contendo o extrato mole obtido. O extrato mole foi caracterizado segundo os testes farmacopeicos e obteve 82,02% (m/m) de teor de sólidos, e o teor de furanocumarinas totais expressas em psoraleno e bergapteno que foi 2,93% (m/v) (58,8 μg/g de psoraleno e bergapteno). Obtiveram-se três diferentes formulações de comprimidos por previa granulação por via úmida, contendo o extrato mole padronizado. Em cada formulação variou-se a proporção dos diluentes celulose microcristalina (MCC) e amido. A compressão foi feita por meio de uma prensa hidráulica e efetuou-se o controle do processo para o estabelecimento das condições de compressão. A metodologia analítica foi covalidada para quantificação de furanocumarinas totais nos comprimidos obtidos, e a concentração de furanocumarinas totais para cada comprimido foi 16800 μg por comprimido.
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Al-Ismail, Deana. "Clinical studies to broaden the application and improve the safety of psoralen and ultraviolet A (PUVA) phototherapies." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/100479/.
Повний текст джерелаАнотація:
This medical doctorate thesis contains clinical studies to broaden the application and to improve the safety and efficacy of ultraviolet (UV) A phototherapies, the main focus being to enhance the current clinical practice of topical psoralen photochemotherapy (PUVA). The thesis includes three studies: 1. The validation of a semi-automated Minimal Phototoxic Dose (MPD) Tester for topical photochemotherapy Thirty seven psoriasis patients referred to the phototherapy unit at St. Woolos, Newport were recruited. Patients had two sets of minimal phototoxic dose (MPD) tests performed on symmetrical, contralateral sites on the lower back. MPD test results from a panel of PUVA-lamps with a UV-opaque template and windows were compared to those from the modified hand-held MPD tester. The hand-held MPD results were linearly related to the PUVA-panel MPD results and this was therefore shown to be a convenient and reliable method of assessing MPD. However, the difference in MPD between the PUVA lamp and the modified handheld MPD tester (CFL TL-10 lamp) was much less than predicted from the PUVA action spectrum of previously published studies suggesting that formal re-evaluation of the erythema action spectrum for PUVA was now appropriate.
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Fröbel, Sascha [Verfasser]. "Ultraschnelle Prozesse bei der therapeutisch genutzten Photochemie von Psoralenen in DNA / Sascha Fröbel." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2016. http://d-nb.info/1106381041/34.
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Gaboriau, François. "Etude structurale des altérations photoinduites dans l'ADN par des dérivés monofonctionnels du psoralène." Paris 6, 1989. http://www.theses.fr/1989PA066731.
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Perera, Anthonige Vidya. "Genes Affecting the Repair and Survival of Escherichia coli Following Psoralen-Induced Damage: a DNA Interstrand Crosslinking Agent." PDXScholar, 2015. https://pdxscholar.library.pdx.edu/open_access_etds/2195.
Повний текст джерелаАнотація:
Photoactivated psoralens and other agents that form DNA interstrand crosslinks are highly cytotoxic and are useful in treating a range of diseases, including vitiligo, psoriasis, and some forms of cancer. Unlike many lesions that damage only one strand of the duplex DNA, DNA interstrand crosslinks form covalent bonds with both strands. Thus, repairing these lesions is complicated both by the lack of an undamaged strand to serve as a template for resynthesis following excision, as well as the potential to form double strand breaks if both strands are incised. A number of models have proposed that repair is likely to couple nucleotide excision repair with other repair pathways such as recombination, and/or translesion synthesis. However, several aspects of these models remain speculative, and how these medically relevant lesions are repaired by cells still remains elusive. In this study, I use Escherichia coli as a model organism to characterize which gene products contribute to survival in the presence of psoralen-induced DNA interstrand crosslinks.
In Chapter II, I demonstrate that although nucleotide excision repair initiates repair, not all subunits contribute equally to survival. Notably, uvrC is less sensitive to psoralen-induced damage than either uvrA or uvrB. I found that Cho, an alternative endonuclease, accounts for the increased resistance of uvrC mutants and contributes to survival in the presence of UvrABC. Cho was not required following angelicin treatment, a psoralen derivative that only forms monoadducts, suggesting that Cho function is specific for interstrand crosslink repair. However, Cho, by itself, is not required for the initial incision and only modestly enhances the rate that psoralen crosslinks are incised in vivo.
Following incision, many of the intermediates in the repair process remain speculative. In Chapter III, I examine how recombination and translesion synthesis mutants contribute to survival of psoralen-induced damage. I show that both recBC and recF contribute to survival, but that neither mutant is as hypersensitive as recA, potentially suggesting that pathways involving either single strand gaps or double strand break intermediates can occur during repair. Finally, I show that Polymerase V is responsible for the translesion synthesis that contributes to survival in the case of psoralen-induced damage in E.coli.
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Guy, Julia. "Photochimiothérapie cutanée : Synthèse de deux molécules hybrides "psoralène-lactone" et études physico-chimiques et photochimiques de leurs interactions avec l'ADN." Université Louis Pasteur (Strasbourg) (1971-2008), 2005. http://www.theses.fr/2005STR13172.
Повний текст джерелаАнотація:
La photochimiothérapie est un terme générique qui désigne l'administration de médicaments photosensibilisants suivie d'une irradiation dans le spectre UV-visible. Les psoralènes font partie de cette classe de molécules photosensibilisantes et sont couramment utilisés en photomédecine, pour le traitement de nombreuses maladies d'hyperprolifération cutanée, en association avec une irradiation UVA. Cependant, l'apparition d'effets secondaires liés à la phototoxicité cutanée des molécules employées limite leur utilisation en thérapeutique. Afin d'accéder à de nouveaux dérivés de psoralène potentiellement utilisables en photochimiothérapie cutanée, nous avons synthétisé deux molécules hybrides basées sur le squelette noyau psoralène, bras espaceur, motif--méthylène--butyrolactone. Différentes études biologiques ont permis de mettre en évidence deux propriétés majeures de ces hétérodimères pour leur utilisation en photochimiothérapie cutanée : ils sont dépourvus de phototoxicité cutanée et ont présenté des activités antiprolifératives élevées sur trois lignées de cellules cancéreuses humaines et notamment sur celle du mélanome malin. Afin de caractériser la nature des interactions existant entre ces molécules et l'ADN, nous avons réalisé des expériences de physicochimie et de photochimie sur des complexes hétérodimères-ADN avant et après irradiation UV. Ces études semblent indiquer que dans leur état fondamental les dérivés "psoralène-lactone" s'intercalent dans l'ADN et provoquent une courbure du grand axe de celui-ci. Après irradiation UV, il semblerait que ces dérivés soient capables de ponter la double hélice en formant des cross-linksPhotochemotherapy is the therapeutic use of radiation in combination with a photosensitizing chemical. Psoralens are well-known photosensitizing drugs which have been employed in photomedicine, in association with UVA radiation, to cure a number of hyperproliferative skin disorders. This therapeutic treatment is generally called PUVA, from psoralen plus UVA light. Nevertheless, the existence of some undesired phototoxic side effects limits the therapeutic use of psoralens. In recent years, many psoralen derivatives have been synthesized with the aim of weakening the phototoxicity on skin. Thus, we report the synthesis and the studies of DNA interactions of two psoralen-lactone heterodimers, which are unable to induce skin phototoxicity on mice and show significant antiproliferative activity on three human cancer cell lines. With the aim of understanding the behaviour of both hybrids toward DNA, we have realized physicochemical and photochemical experiments on heterodimers-DNA complexes. We have shown that, in the dark both hybrids are able to intercalate between DNA base pairs and seem to induce DNA bending. After UV radiation, both compounds exhibit a remarkable ability to give rise to cross-links with double stranded DNA
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Huckel, Stahli Valérie. "Les psoralènes, interaction, mode d'action, effets secondaires et ressources naturelles." Nancy 1, 1996. http://www.theses.fr/1996NAN1A037.
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Gontcharov, Julia [Verfasser], and Wolfgang [Akademischer Betreuer] Zinth. "Reaktionen von Pyrimidin-Dimeren und Psoralen im Triplett-Kanal : Infrarotspektroskopie von CPD-Bildung und Photoaddition / Julia Gontcharov ; Betreuer: Wolfgang Zinth." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2021. http://d-nb.info/1236502353/34.
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Seiller, Nathalie. "Les psoralènes : mécanisme d'action, intérêts et toxicitlé." Paris 5, 1994. http://www.theses.fr/1994PA05P138.
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LAQUERBE, AGNES. "Signature moleculaire des photolesions d'un psoralene dans les cellules humaines normales et d'anemie de fanconi. Etudes des mecanismes a l'origine des deletions." Paris 7, 1995. http://www.theses.fr/1995PA077218.
Повний текст джерелаАнотація:
L'analyse des spectres des mutations induites par un agent genotoxique permet de rechercher une signature specifique a cet agent et d'obtenir des informations sur le(s) mecanisme(s) implique(s) dans la formation des mutations. Les psoralenes bifonctionnels, utilises en photochimiotherapie de maladies cutanees, produisent en presence de rayonnement uva des monoadditions et des pontages interbrins de l'adn. L'analyse des mutations au niveau du gene hprt nous a permis de demontrer que dans les cellules humaines normales, le mecanisme mutagene majeur operant sur les lesions des psoralenes est la synthese translesionnelle. La majorite des substitutions de base qui en resultent, sont situees sur des thymines dans un contexte 5'-tpa, sites de photolesions des psoralenes. Les photoadduits de psoralene laissent donc au niveau d'un gene endogene une signature moleculaire hautement specifique. Une analyse similaire a ete menee dans des cellules de patients atteints d'anemie de fanconi (af), maladie hereditaire predisposant au cancer. Les cellules af se caracterisent par une instabilite chromosomique et des anomalies dans la gestion des lesions induites par les agents pontant l'adn. Dans les cellules af, a l'inverse des cellules normales, les deletions representent la classe predominante des mutations. Ces cellules constituent donc un modele de choix pour l'etude des mecanismes impliques dans la formation de ce type de mutations. L'analyse des sequences au niveau des jonctions des deletions a revele que: (i) des deletions emportant les memes exons ont lieu au meme site, (ii) deux deletions de taille differente ont un point de rupture identique, (iii) des motifs heptameres identiques ou similaires a la sequence consensus qui sert de signal lors de la recombinaison v(d)j, sont presents aux jonctions des deletions. Ceci suggere qu'une recombinaison illegitime apparentee a la recombinaison v(d)j, processus intervenant dans les rearrangements des genes des immunoglobulines, pourrait etre responsable des deletions dans les cellules af
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Menilli, Luca. "Evaluation of the activity of photoactivatable compounds under different irradiation conditions on human cancer cell lines for photochemotherapeutic applications." Doctoral thesis, Università degli studi di Padova, 2019. http://hdl.handle.net/11577/3422697.
Повний текст джерелаАнотація:
ABSTRACT
During these 3 years of PhD course, my research activity has focused on the evaluation of the antiproliferative activity of known photosensitizing compounds, using activation under different selected wavelengths.
Evaluation of 8-Methoxypsoralen (8-MOP) and 4,6,6’-Trimethylangelicin (TMA) antiproliferative activity in combination with Blue Light irradiation
Psoralens and angelicins are known photosensitizing agents, used in combination with UVA light (PUVA) for the treatment of a variety of diseases (i.e. psoriasis, vitiligo, mycosis fungoides, Graft-versus-Host disease, cutaneous T-cell lymphoma). Although this therapeutic approach proved to be highly effective, side effects may occur with PUVA therapy, including skin cancer (squamous cell carcinoma and basal cell carcinoma). The use of UVA irradiation also limits the light penetration into tissues, restricting the application of this therapeutic approach to superficial areas and it is known to cause DNA damages.
Previous studies indicated that psoralens can be activated with longer wavelengths (417 nm), with a reduced formation of mutagenic lesions, such as DNA crosslinks. These evidences gave us the idea to use blue light (BL) for the activation of psoralens, in order to reduce the toxicity of the treatment and to extend the application of this therapeutic approach to solid tumors as BL is also more penetrating than UVA.
Thus, the antiproliferative activity of 8-MOP and TMA was evaluated in combination with blue light on DU145 human prostate cancer cell line, along with the detection of DNA damages, ROS generation inside the cells and western blot analysis of proapoptotic, prosurvival and proliferative molecular pathways. Flow cytometry was used for the determination of cell death mechanism and to analyse the expression of CD44 receptors, which are markers for stem cell features.
Potential anticancer activity of Fluphenazine activated with UVA light
Fluphenazine (FPZ) is an antipsychotic agent from the phenothiazine family. It exerts its activity by blocking postsynaptic D2 dopamine receptors in the limbic, cortical system and basal ganglia areas of the brain. Blocking the action of dopamine, it reduces the hallucinations and delusions that are associated with schizophrenia. FPZ has a wide adverse effect profile, including extrapyramidal symptoms (akathisia, tremors, dyskinesia). In particular, fluphenazine induces photosensitization in patients exposed to sunlight as adverse effect.
Exploiting this last side effect of FPZ under light exposure, its cytotoxic activity in combination with UVA light was investigated on three different cell line.
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DEMARET, JEAN PHILIPPE. "Utilisation conjointe des techniques de graphisme, mecanique et dynamique moleculaires en modelisation moleculaire : application aux intercalants adn-psoralene et aux phospholipases a#2." Paris 6, 1989. http://www.theses.fr/1989PA066138.
Повний текст джерелаАнотація:
Nous avons utilise les techniques de modelisation et de dynamique moleculaires pour l'etude de deux problemes: 1) l'etude des contraintes imposees par l'helice d'adn sur la geometrie des complexes non covalents adn-psoralene: l'elaboration de nouveaux composes de type benzofuranne, derives des psoralenes. 2) l'etude dynamique de phospholipases a#2 et des residus impliques dans leur activite catalytique; la modelisation de la phospholipase a#2 extraite du venin du serpent naja nigrocollis
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Sai͏̈d, Abdou Elmadjid. "Contribution à l'étude de la relation structure-activité des psoralènes utilisés en thérapeutique." Besançon, 1996. http://www.theses.fr/1996BESA3502.
Повний текст джерела
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Salahou, Adama. "Analyse radiocristallographique de molécules antitumorales (Ellipticinium) et photosensibilisantes (Psoralène) : étude de la cristallisation avec des fragments d'acides nucléiques." Bordeaux 1, 1987. http://www.theses.fr/1987BOR10515.
Повний текст джерела
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Salahou, Adama. "Analyse radiocristallographique de molécules antitumorales (Ellipticinium) et photosensibilisantes (psoralène) étude de la cristallisation avec des fragments d'acides nucléiques /." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37609632t.
Повний текст джерела