Três fungos endofíticos isolados de Viguiera robusta (Asteraceae) foram cultivados em três meios de cultivo distintos (Czapek, arroz e extrato de malte) e também em culturas binárias em extrato de malte. Para a extração dos cultivos em extrato de malte foi utilizada a resina diaion HP-20, que promove a adsorção dos metabólitos produzidos pelo fungo, aumentando o rendimento dos extratos. Os extratos e frações obtidos foram submetidos à análise química por meio de técnicas cromatográficas e RMN 1H e a ensaios diversos biológicos para a comparação de seus perfis. O estudo químico do extrato de Chaetomium globosum (VR-10), cultivado em arroz, levou a isolamento da substância S1 (chaetoglobosina E), que apresenta elevada atividade citotóxica e é uma ferramenta importante em biologia química. Também de C. globosum foi isolado a substância S2 (dimetil-tereftalato), o qual já foi identificado como metabólito de fungo endofítico e também de planta. De Pestalotiopsis guepini (VR-8), cultivado em Czapek, foi isolada a substância S3 (tirosol), relatado na literatura como molécula sinalizadora em Candida albicans. Do fungo Cladosporium sphaerospermum (VR-2), após cultivo em arroz, foram isoladas três substâncias: marcfortina A (S4), a marcfortina B (S5) e a marcfortina C (S6) e (S7), substâncias com pronunciada atividade antiparasitária. Foi desenvolvido um método via CLAE-DAD-MS/MS para identificação rápida de derivados de marcfortina, o qual possibilitiou a identificação da substância S7 (marcfortina D) no extrato bruto de C. sphaerospermum. A análise conformacional da marcfortina A (S4) foi realizada através de experimentos de NOE-diff e técnicas de modelagem molecular. Os resultados obtidos nos bioensaios após diferentes cultivos dos fungos endofíticos indicaram que estes são fontes promissoras de substâncias bioativas, constituindo ferramentas importantes na busca por novos compostos. / Three endophytic fungi isolated from Viguiera robusta (Asteraceae) were cultivated in three different culture media (Czapek, rice and malt extract) and also in mixed cultures in the malt extract medium. Diaion HP-20 resin was used for the malt extract cultures extraction increasing the yields of the extracts. Extracts and fractions have been submitted to chemical analyses by chromatographic techniques and 1H NMR, and also to several bioassays for the comparison of their chemical and biological profiles. Chemical study of the rice culture extract from Chaetomium globosum (VR-10) gave the citotoxic compound S1 (chaetoglobosin E), an important chemical biology tool. C. globosum also led to the isolation of compound S2 (dimethyl-terephthalate), previously isolated from an endophytic fungus and also from plants. Compound S3 (tyrosol) has been isolated from the Czapek culture extract of Pestalotiopsis guepini (VR-8). Tyrosol has been reported as a quorum sensing molecule in Candida albicans. Three compounds have been isolated from Cladosporium sphaerospermum (VR-2) rice cuture extract: marcfortine A (S4), marcfortine B (S5) and marcfortine C (S6). Marcfortines have been reported as potent antiparasitic compounds. A HPLC-DAD-MS/MS was developed for the rapid identification of marcfortine derivatives, which allowed the identification of compound S7 (marcfortine D) in the crude extract from C. sphaerospermum. The conformational analysis of marcfortine A (S4) was carried out by NOE-diff experiments and molecular modeling techniques. Bioassays results showed that the endophytic fungi should be considered as promising sources of novel and bioactive compounds.

Neste estudo, foram sintetizados complexos de ródio com aminoácidos e aminoácidos N-protegidos. Os compostos sintetizados foram caracterizados por análise elementar, espectrofotometria nas regiões do infravermelho e ultravioleta-visível, susceptibilidade magnética, ressonância magnética nuclear de próton e calorimetria exploratória diferencial. As técnicas analíticas utilizadas permitiram avaliar a estrutura dos complexos de ródio obtidos. Nos complexos sintetizados com aminoácidos, a ligação ocorreu pelos átomos de nitrogênio do grupamento amina e pelo oxigênio do grupo carboxila, formando anéis quelato de cinco membros, estrutura esta distinta da apresentada por compostos diméricos de ródio (II). Este modo de coordenação típico de carboxilatos de ródio dimérico, foi alcançado fazendo-se o bloqueio do grupamento amino, direcionando assim a coordenação do aminoácido, aos átomos de ródio, através dos dois oxigênios da carboxila. Numa etapa posterior, o grupo protetor foi removido por ataque ácido, tomando o complexo, anteriormente solúvel em solventes apoiares, totalmente solúvel em água, sendo mantida a estrutura de gaiola. Partindo-se dos complexos de ródio (II) sintetizados com aminoácidos N-bloqueados, foram obtidos adutos com o ácido isonicotínico, que se mostraram mais hidrossolúveis do que os complexos iniciais. Os compostos [Rh2(Boc-Gly)4)(I), [Rh2(Boc-L-Ala)4)(II) e seus respectivos adutos com o ácido isonicotínico foram submetidos a ensaios biológicos in vitro, onde foi avaliada a citotoxicidade destes sobre células tumorais K562, U937 e de tumor de Ehrlich. O aduto [Rh2(Boc-L-Ala)4](AIN)2(III) também foi submetido a um ensaio in vivo, de sobrevida. Camundongos portadores de tumor ascite de Ehrlich, tratados com solução do complexo (III), tiveram um aumento significativo de sobrevida, com formação de tumor sólido. Os complexos (I), (II), [Rh2(Boc-L-Val)4)(IV), [Rh2(Boc-L-Leu)4](V) e [Rh2(Boc-D-Phe)4)(VI) foram avaliados quanto ao seu potencial catalítico, em reações de hidrogenação. Os resultados foram expressos em termos de conversão de substrato em função do tempo de reação, número de rotação, freqüência de rotação e curvas TT x TTG. O complexo (I) apresentou atividade semelhante ao acetato de ródio (II), que foi utilizado como complexo de referência. Os demais compostos, (II), (V) e (VI) mostraram-se mais ativos que o acetato de ródio (II), nas reações de hidrogenação de hexeno-1 em etanol. / In this study, rhodium complexes were synthesized using amino acids and N-protected amino acids as ligands. The synthesized compounds were characterized by elemental analysis, IR and UVVis spectroscopy, magnetic susceptibility, proton magnetic nuclear resonance and diferential scanning calorimetry. The used analytical techniques allowed us to evaluate the structure of the obtained rhodium complexes. In the amino acids complexes, the binding occured through nitrogen atoms of the amino group and through the oxygen atom of the carboxyl group, forming chelate rings of five members, being these structures different from those presented by rhodium (II) carboxylates. This coordination mode was achieved protecting the amino group. In a next stage, the protecting group was removed by acid attack, turning the previously soluble in apolar solvents complex, totally soluble in water, being maintained the cage structure. From the N-protected amino acids rhodium (II) complexes synthesized, we obtained the isonicotinic acid adducts, more hydrossoluble than the original complexes. Antitumor activity of rhodium complexes [Rh2(Boc-Gly)4](I), [Rh2(Boc-L-Ala)4](II) and its isonicotinic acid adducts, was evaluated in vitro ( cell cultures K562, U937 and Ehrlich) and the compound [Rh2(Boc-L-Ala)4](AIN)2(III) was also submitted to a in vivo assay. Mices bearing Ehrlich ascite tumor, when treated with complex (III) solution, had a significant increase life span, with formation of solid tumor. The complexes (I), (II), [Rh2(Boc-L-Val)4](IV), [Rh2(Boc-L-Leu)4](V) and [Rh2(Boc-D-Phe)4](VI) were also tested in catalytic hydrogenation reactions. The results were expressed in terms of substrate conversion, turnover number, turnover frequency and TT x TTG curves. The complex (I) presented catalytic activity similar to the rhodium acetate (II), that was used as reference complex. The other compounds, (II), (V) and (I) exhibited improved catalytic behavior compared to rhodium (II) acetate in hydrogenation reactions using 1-hexene as substrate.

O câncer é uma das doenças que mais acometem a população no mundo. Dessa forma, estudar suas terapêuticas é importante para o entendimento dos mecanismos e alvos biológicos por detrás da doença. Apesar dos tratamentos convencionais apresentarem uma boa eficácia, eles também provocam respostas indesejadas, como danos moleculares, resistência de células neoplásicas e efeitos colaterais fortes, colaborando para uma maior taxa de reincidência de neoplasias e mortalidade de pacientes. Sendo assim, a busca por alternativas é um importante desafio da Ciência Moderna para aprimorar e/ou substituir esses tratamentos. As plantas medicinais, como alternativa, são o foco de muitos estudos voltados ao câncer. O objetivo do presente trabalho foi avaliar o efeito citotóxico de 59 extratos em linhagens celulares humanas de câncer de mama (MDA-MB-231 e MCF7), próstata (PC-3 e DU 145) e fígado (HepG2). Foi realizada, inicialmente, uma triagem dos extratos por MTT em duas diluições 100x e 1000x para análise da viabilidade celular desses extratos. No total, 35 extratos obtiveram uma resposta para, pelo menos, uma das linhagens de câncer. A próxima etapa envolveu estudar os extratos pré-seletivos na triagem através de curvas-resposta quantificando a seletividade desses extratos para cada linhagem testada. Para essa etapa, foram selecionados 31 extratos. No câncer de mama, para a linhagem MDA-MB-231 nove extratos foram seletivos, e para MCF7 foram seis extratos. No câncer de próstata, para a linhagem PC-3, quinze extratos foram seletivos, e para DU 145 dezesseis extratos foram seletivos, mostrando uma maior sensibilidade do câncer de próstata comparado ao câncer de mama e fígado (HepG2 - sete extratos seletivos) em relação aos extratos testados. De todos os resultados apresentados, algodão de seda (Calotropis procera), camomila (Matricaria chamomilla), casca de anta (Drimys winteri), erva de São Caetano (Momordica charantia L.), estigmas de milho (Zea mays), graviola (Annona muricata), ipê roxo (Tabebuia sp.), malva - folhas (Malva sylvestris) e unha de gato (Uncaria tomentosa) foram os extratos mais amplamente significativos atingindo as linhagens celulares apresentando altos índices de seletividade. Com a realização desse trabalho podemos concluir que os extratos apresentam atividade antiproliferativa e seus fitoquímicos podem ser utilizados no estudo de novos fitoterápicos. O próximo passo é elucidar os mecanismos moleculares onde eles atuam. / Cancer is one of the most common diseases overworld. Studying the therapeutics of it is important to understand the biological mechanisms and targets behind this disease. Although conventional treatments show a good outcome against some types of cancer, they also currently cause undesired responses, such as molecular damage, neoplastic cell resistance and strong side effects, increasing recurrence of neoplasms, metastasis formation, and patient mortality. Therefore, the search for new alternatives is a challenge for Modern Science to improve or replace conventional treatments. In view of their antiproliferative effects medicinal plants have become the focus of many cancer studies as an alternative. The aim of the present study was to evaluate the cytotoxic and antiproliferative effect of 59 plant extracts in human cancer cell lines as breast cancer (MDA-MB-231 and MCF7), prostate cancer (PC-3 and DU 145) and liver cancer (HepG2). Initially, the extracts were screened in two different dilutions 100x and 1000x by MTT to analyze the cellular viability and cytotoxicity effects of them. To 59 extracts analyzed, 35 were effective against at least one of the tested lineages. The next step involved studying those pre-selective extracts through response curves to quantify the selectivity of these extracts for each cell lineage tested. For this stage, 31 extracts were selected. In breast cancer, for MDA-MB-231, nine extracts were selective and for MCF7 were six extracts. In prostate cancer, for PC-3, fifteen extracts were selective and for DU 145 were sixteen extracts. For liver cancer (HepG2) only seven extracts were selective. Comparing all the cancer lineages we can see a greater sensitivity of prostate cancer lineages compared to breast cancer and liver cancer in response of these tested extracts. Of all the results presented, silk cotton (Calotropis procera), chamomile (Matricaria chamomilla), winter\'s bark (Drimys winteri), bitter melon (Momordica charantia L.), corn silk (Zea mays), graviola (Annona muricata), purple trumpet tree (Tabebuia sp.), malva - folhas (Malva sylvestris) e unha de gato (Uncaria tomentosa) silk cotton (Calotropis procera), chamomile (Matricaria chamomilla), graviola (Annona muricata) and mallow-leaves (Malva sylvestris) were the most effective extracts reaching different cell types and present high selectivity indices. With the accomplishment of this work we can conclude that the natural extracts of plants presented antiproliferative activity in cancer lines and their phytochemicals can be used to study new herbal medicines. The next step, then, is to understand the molecular mechanisms where they act.

Made available in DSpace on 2014-12-17T14:16:31Z (GMT). No. of bitstreams: 1 ReginaCE_DISSERT.pdf: 2319971 bytes, checksum: 40c841a1d50cf6f734095c894d9d920d (MD5) Previous issue date: 2013-04-25 / Homeopathic medicines have been used for over two hundred years without the examination of their effects on in vivo and in vitro assays, due to the peculiarity of homeopathic preparations, the high dilution, which creates a challenge for the use of usual analytical techniques of quality control of medicine.Although there is scarcity of literature and variety of experiments, recently there have been some studies with few in vitro assays which have shown positive responses when evaluating the mechanism of action of homeopathic medicines which are able to act on a specific system.The present study aims to evaluate the efficacy of homeopathic products containing Momordica charantia through bioassays.Homeopathic products were tested by the MTT to assess cytotoxicity in RAW 264.7 (macrophage-like cells) and in tumor cells HeLa (human cervical adenocarcinoma cells), CHO K1 (Chinese hamster ovary cells), PANC-1 (human pancreas cancer cells) and PC-3 (human prostate cancer cells), dosage of inflammatory mediators NO, TNF-? and IL-6 released by RAW 264.7 cells, analysis of the death process and cell cycle changes of PC-3 by flow cytometry. The data demonstrate that homeopathic products of Momordica charantia did not show cytotoxicity to RAW 264.7, increased the production of inflammatory mediators by RAW 264.7 synergistically with LPS, showed cytotoxicity to PC-3 with change in its cell cycle inhibiting its proliferation, being the 30CH the most potent sample. Correlation studies were conducted in order to evaluate the possible in vitro applicable models to the quality control of homeopathic products with Momordica charantia. The data showed that the best applicable models in assessing the quality are the MTT to assess cytotoxicity in RAW 264.7 and PC-3 in 24 hours for Momordica charantia fruit products and dosage of NO production by RAW 264.7 with and without LPS / Os medicamentos homeop?ticos t?m sido utilizados por mais de duzentos anos, sem a verifica??o dos seus efeitos em ensaios in vivo e in vitro. Devido ? peculiaridade das prepara??es homeop?ticas, sua alta dilui??o, que cria um desafio para a utiliza??o das t?cnicas anal?ticas usuais do controle de qualidade de medicamentos. Embora exista escassez de literatura e heterogeneidade de experimentos, recentemente existem alguns estudos com poucos ensaios in vitro que t?m apresentado respostas positivas quando se avalia o mecanismo de a??o dos medicamentos homeop?ticos que s?o capazes de atuar em um sistema espec?fico. O presente estudo visa ? avalia??o da efic?cia dos produtos homeop?ticos contendo Momordica charantia atrav?s de bioensaios. Os produtos homeop?ticos foram avaliados pelo teste do MTT para verifica??o da citotoxicidade em RAW 264.7(macr?fago murino) e em c?lulas tumorais HeLa (Adenocarcinoma cervical uterino humano), CHO K1 (C?lulas de ov?rio de Hamster chin?s), PANC-1 (Carcinoma de p?ncreas humano) e PC-3 (Adenocarcinoma de pr?stata humano); pela dosagem de mediadores da inflama??o NO, TNF-? e IL-6 liberados por c?lulas RAW 264.7 e pela an?lise do processo de morte e da altera??o do ciclo celular de PC-3 por citometria de fluxo. Os dados demonstraram que os produtos homeop?ticos de Momordica charantia n?o apresentaram citotoxicidade para RAW 264.7, aumentaram a produ??o dos mediadores da inflama??o por RAW 264.7 sinergicamente com LPS, mostraram citotoxicidade para PC-3 com altera??o no seu ciclo celular inibindo sua prolifera??o, sendo 30CH a amostra mais potente. Foram realizados estudos de correla??o visando avaliar os poss?veis modelos in vitro aplic?veis ao controle de qualidade de produtos homeop?ticos contendo Momordica charantia. Os dados demonstraram que os melhores modelos aplic?veis na avalia??o da qualidade s?o o teste do MTT para avaliar citotoxicidade em RAW 264.7 e PC-3 em 24 horas para os produtos de Momordica charantia (fr) e dosagem da produ??o de NO por RAW 264.7 com e sem LPS

La combrétastatine A-4 est un produit naturel isolé d'un arbuste africain Combretum caffrum et qui possède de très intéressantes propriétés biologiques: inhibition de la polymérisation de la tubuline et propriétés antiprolifératives auprès de nombreuses cellules tumorales. Malheureusement, ce produit possède de propriétés pharmacocinétiques non optimales qui limitent son application clinique. Par conséquent de nombreux dérivés synthétiques ont été testés et parmi ceux-ci, l'isocombrétastatine A-4 (isoCA-4). Dans notre travail de thèse, nous avons donc synthétisé des analogues de l'isoCA-4 dont un des cycles aromatiques a été remplacé par des hétérocycles thiophènes et benzothiophènes diversement substitués. Certains de ces produits ont montré des activités du même ordre que la colchicine, substance de référence sur la polymérisation de la tubuline, et sur la prolifération de cellules mélanocytaires IC8. Les composés présentant une structure benzo[b]thiophène montrent une meilleure activité que ceux ayant une simple structure thiophène. De plus, les composés portant une chaine latérale en position 2 montrent une activité supérieure à ceux substitués en position 3.D'autre part, les stuctures indénoindoles sont connues comme étant de puissants inhibiteurs de la caséine kinase 2 (CK2), celle-ci joue un rôle important dans de nombreux processus cellulaires. A partir de cette structure indénoindole et, en utilisant une stratégie proche de celle utilisée pour la série précédente (par introduction d'un atome d'iode en position ortho et cyclisation pallado-catalysée), nous avons synthétisé des analogues indénohétérocycliquesen remplaçant le noyau indolepar des noyauxthiophèneetbenzo[b]thiophène. L'activité inhibitrice de ces dérivés vis-à-vis de la CK2 a été évaluée et l'un de ces composés a montré une forte activité / Isocombretastatin A-4 (isoCA-4), a modified combretastatin A-4 (CA-4), was recently discovered known as a strong activity compound to inhibit tubulin polymerization. The vinyl derivatives opened a new series which is hardly exploited. Based on the structure of isoCA-4, we synthesized isoheterocycles series by replacing the B-ring of isoCA-4 by thiophene and benzo[b]thiophene derivatives. These two series were evaluated in their ability to inhibit tubulin assembly. The benzo[b]thiophene derivativesshowed better activity than thiophene derivatives, the binding position 2 of benzo[b]thiophene showed higher activity than position 3. Indenoindoles was known as a potent series to inhibit casein kinase 2 which plays important role in many processes in cell. Based on the structure of indenoindole, we synthesized indenoheterocycles by replacing indole by thiophene and benzo[b]thiophene derivatives. These two series were evaluated in their ability to inhibit CK2. One of the compoundsshowed high activity

O câncer é uma das doenças que mais acometem a população no mundo. Dessa forma, estudar suas terapêuticas é importante para o entendimento dos mecanismos e alvos biológicos por detrás da doença. Apesar dos tratamentos convencionais apresentarem uma boa eficácia, eles também provocam respostas indesejadas, como danos moleculares, resistência de células neoplásicas e efeitos colaterais fortes, colaborando para uma maior taxa de reincidência de neoplasias e mortalidade de pacientes. Sendo assim, a busca por alternativas é um importante desafio da Ciência Moderna para aprimorar e/ou substituir esses tratamentos. As plantas medicinais, como alternativa, são o foco de muitos estudos voltados ao câncer. O objetivo do presente trabalho foi avaliar o efeito citotóxico de 59 extratos em linhagens celulares humanas de câncer de mama (MDA-MB-231 e MCF7), próstata (PC-3 e DU 145) e fígado (HepG2). Foi realizada, inicialmente, uma triagem dos extratos por MTT em duas diluições 100x e 1000x para análise da viabilidade celular desses extratos. No total, 35 extratos obtiveram uma resposta para, pelo menos, uma das linhagens de câncer. A próxima etapa envolveu estudar os extratos pré-seletivos na triagem através de curvas-resposta quantificando a seletividade desses extratos para cada linhagem testada. Para essa etapa, foram selecionados 31 extratos. No câncer de mama, para a linhagem MDA-MB-231 nove extratos foram seletivos, e para MCF7 foram seis extratos. No câncer de próstata, para a linhagem PC-3, quinze extratos foram seletivos, e para DU 145 dezesseis extratos foram seletivos, mostrando uma maior sensibilidade do câncer de próstata comparado ao câncer de mama e fígado (HepG2 - sete extratos seletivos) em relação aos extratos testados. De todos os resultados apresentados, algodão de seda (Calotropis procera), camomila (Matricaria chamomilla), casca de anta (Drimys winteri), erva de São Caetano (Momordica charantia L.), estigmas de milho (Zea mays), graviola (Annona muricata), ipê roxo (Tabebuia sp.), malva - folhas (Malva sylvestris) e unha de gato (Uncaria tomentosa) foram os extratos mais amplamente significativos atingindo as linhagens celulares apresentando altos índices de seletividade. Com a realização desse trabalho podemos concluir que os extratos apresentam atividade antiproliferativa e seus fitoquímicos podem ser utilizados no estudo de novos fitoterápicos. O próximo passo é elucidar os mecanismos moleculares onde eles atuam. / Cancer is one of the most common diseases overworld. Studying the therapeutics of it is important to understand the biological mechanisms and targets behind this disease. Although conventional treatments show a good outcome against some types of cancer, they also currently cause undesired responses, such as molecular damage, neoplastic cell resistance and strong side effects, increasing recurrence of neoplasms, metastasis formation, and patient mortality. Therefore, the search for new alternatives is a challenge for Modern Science to improve or replace conventional treatments. In view of their antiproliferative effects medicinal plants have become the focus of many cancer studies as an alternative. The aim of the present study was to evaluate the cytotoxic and antiproliferative effect of 59 plant extracts in human cancer cell lines as breast cancer (MDA-MB-231 and MCF7), prostate cancer (PC-3 and DU 145) and liver cancer (HepG2). Initially, the extracts were screened in two different dilutions 100x and 1000x by MTT to analyze the cellular viability and cytotoxicity effects of them. To 59 extracts analyzed, 35 were effective against at least one of the tested lineages. The next step involved studying those pre-selective extracts through response curves to quantify the selectivity of these extracts for each cell lineage tested. For this stage, 31 extracts were selected. In breast cancer, for MDA-MB-231, nine extracts were selective and for MCF7 were six extracts. In prostate cancer, for PC-3, fifteen extracts were selective and for DU 145 were sixteen extracts. For liver cancer (HepG2) only seven extracts were selective. Comparing all the cancer lineages we can see a greater sensitivity of prostate cancer lineages compared to breast cancer and liver cancer in response of these tested extracts. Of all the results presented, silk cotton (Calotropis procera), chamomile (Matricaria chamomilla), winter\'s bark (Drimys winteri), bitter melon (Momordica charantia L.), corn silk (Zea mays), graviola (Annona muricata), purple trumpet tree (Tabebuia sp.), malva - folhas (Malva sylvestris) e unha de gato (Uncaria tomentosa) silk cotton (Calotropis procera), chamomile (Matricaria chamomilla), graviola (Annona muricata) and mallow-leaves (Malva sylvestris) were the most effective extracts reaching different cell types and present high selectivity indices. With the accomplishment of this work we can conclude that the natural extracts of plants presented antiproliferative activity in cancer lines and their phytochemicals can be used to study new herbal medicines. The next step, then, is to understand the molecular mechanisms where they act.

Made available in DSpace on 2016-12-23T13:51:45Z (GMT). No. of bitstreams: 1 Flavia Maria Silva Brito.pdf: 1958233 bytes, checksum: 19806ba42f2c6acb72b77967069c2d99 (MD5) Previous issue date: 2013-02-26 / Este trabalho teve como objetivos avaliar as características anatômicas e físicas do bambu in natura , analisar os efeitos da termorretificação nas propriedades tecnológicas do bambu laminado colado termorretificado (BLCTR) e na sua durabilidade natural. Foram coletados quatro colmos em idade adulta e cortados a cada 2,0 m, divididos em quatro secções no sentido longitudinal sendo imersas em água durante 10 dias e secas ao ar. As secções foram transformadas em taliscas com dimensões de 0,5 x 3,5 x 45 cm (espessura x largura x comprimento) e tratadas termicamente a 100, 140, 160, 180 e 200°C, durante uma hora para cada temperatura. Os adesivos utilizados foram o Cascophen RS-216-M , à base de resorcinol - formaldeído, Cascamite PL-2030 , à base de uréia - formaldeído, ambos termofixos e um termoplástico à base de acetato de polivinila, Cascorez 2500 . As taliscas termorretificadas foram dimensionadas conforme cada ensaio realizado. Observou-se que os colmos de bambu possuem uma frequência de vasos de 0 a 4 vasos.mm-2 com média de 2 vasos.mm-², fibras longas e estreitas com comprimento médio de 2,72 mm. A massa específica básica de 0,66 g.cm-3 e a retratibilidade volumétrica de 15,41%. Os teores de extrativos e lignina total aumentaram, conforme o incremento da temperatura, e o teor de holocelulose foi reduzido. A partir da temperatura de 160 °C ocorreu um ganho na durabilidade natural do bambu e na estabilidade dimensional do BLCTR aderido com RF, porém houve uma queda nos valores da massa específica básica e na resistência mecânica do material / This work aimed to evaluate the physical and anatomical characteristics of bamboo "in natura", analysing the effects of thermal treatment on the technological properties of glued laminated bamboo thermo-modified (GLBT) and in your natural durability. A total of four culms were collected in age adulthood and cut every to 2.0 m and divided into four lengthwise sections that were immersed in water for 10 days and air-dried. The sections were transformed into flights with dimensions of 0.5 x 3,5 x 45 cm (thickness x width x length) and thermal treated to 100, 140, 160, 180 and 200 °C for one hour for each temperature. T he adhesives used were Cascophen RS-216-M , based resorcinol formaldehyde, Cascamite PL-2030 , based on urea - formaldehyde, both thermoset and thermoplastic based on one polyvinylacetate, Cascorez 2500 . The flights thermal treated were scaled according to each proposed test. It was observed that the bamboo culms have a frequency of 0 to 4 vessels.mm-2, whith mean of vessels.mm-2, with long and narrow fibres with length average of 2.72 mm. The basic specific gravity was of 0.66 g.cm-3 and volumetric shrinkage of 15.41%. The total extractives and lignin contents increased as the temperature increase, and holocellulose content has been reduced. Since the temperature of 160 °C was a gain in durability natural bamboo and the dimensional stability of GLBT adhered to RF, but there was a decrease in the values of specific gravity and mechanicalproperties of the material

<p>The rapid analysis of complex samples using mass spectrometry (MS) provides valuable information in both point-of-care (e.g. drug testing) and laboratory-based applications, including the generation of spectral libraries for classification of biosamples, the identification of biomarkers through large-scale studies, as well as the synthesis and bioactivity assessments of large compound sets necessary for drug discovery. In all these cases, the inherent speed of MS is attractive, but rarely fully utilized due to the widespread use of sample purification techniques prior to analysis. Ambient ionization methodologies can help circumvent this drawback by facilitating high-throughput qualitative and quantitative analysis directly from the complex samples without any need for work-up. For instance, the use of swabs or paper substrates allows for rapid identification, quantification, and confirmation, of drugs of abuse from biofluids or surfaces of forensic interest in a matter of minutes, as described in the first two chapters of this dissertation. Faster analysis can be achieved using an automated desorption electrospray ionization (DESI) platform which allows for the rapid and direct screening of complex-sample microarrays with throughputs better than 1 sample per second, giving access to rich spectral information from tens of thousands of samples per day. The development of the bioanalytical capabilities of this platform, particularly within the context of drug discovery (e.g. bioactivity assays, biosample analysis), is described across most other chapters of this dissertation. The use of DESI, a contactless ambient ionization method developed in our laboratory and whose 20 years of history are overviewed in the introduction of this document, provides an additional advantage as the secondary microdroplets generated through the DESI process act as reaction vessels that can accelerate organic reactions by up to six orders of magnitude, facilitating on-the-fly synthesis of new compounds from arrays of starting materials. Unique implications of this microdroplet chemistry in the prebiotic synthesis of peptides and spontaneous redox chemistry at air-solution interfaces, together with its practical applications to the synthesis of new drug molecules, are also overviewed. The success obtained with the first automated DESI-MS system, developed within the DARPA Make It program, led to increased interest in a new-generation platform which was designed over the past year, as overviewed in the last section of this dissertation, and which is currently being installed for validation prior to the transfer of the technology to NCATS, where we anticipate it will make a significant impact through the consolidation and acceleration of the early drug discovery workflow.</p>