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No. of bitstreams: 2 PDF - Deysiane Oliveira Brandão.pdf: 3147875 bytes, checksum: 4e032a8ddfe55546168a4cf23c724b4c (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-02-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Due to the absence of a fully effective intracanal formulation, the search for new drugs from medicinal plants is necessary.In this case the Ximenia americana L., stink plant widely used in traditional medicine as antibacterial, may be used develop new formulations intracanal. However, there is no standardization of their extract by the pharmaceutical industry, with regard to studies of pre-formulation and standardization of analytical techniques to determine its safety, efficacy and quality. In this context, this study aimed to develop from X. americana L. one intracanal paste , with antimicrobial activity, applying parameters validation process for testing and microbiological potency determination of major chemical component, toxicological studies and drug excipient compatibility. Two types of extracts were obtained from the bark of X. American L, hydroalcoholic which was subsequently sprayed in spray dryer and that ethanol extract was concentrated on a rotary evaporator. For determination of antimicrobial activity, used the hidroalcólicos extracts applying the technique of agar / cylinder diffusion. Toxicological tests consisted in acute toxicity and cytotoxicity. Phytochemical analysis was based on quantitative determination of total polyphenols, total flavonoids, tannins condensed and total saponins. The major chemical compound was identified as gallic acid by high performance liquid chromatography efficiency as well as its determination, which was validated according to the official compendia. The validation of microbiological assay was performed X. American compared to standard (gallic acid). The study drug / excipient compatibility was accomplished by applying analytical techniques and term spectroscopy in the infrared region. X. American, showed activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus oralis and Klebsiella pneumoniae. As biosecurity, this plant showed no toxicity in the assays analyzed. Phytochemical analysis showed good concentrations of secondary metabolites. The marker was identified and quantified in the concentration of 12μg/mL. Regarding the microbiological assay, this presented, linearity, accuracy, precision, limits of detection and quantification and robustness. As for the compatibility study excipients that were incompatible in thermoanalytical techniques, spectroscopy, these incompatibilities were not as intense, with respect to removal of functional groups of excipients and the dry extract. Thus studies that show the development of a herbal medicine, as well as the characterization and standardization of the extract of X. American L are important because lack of official methodology that proves the quality, safety and efficacy of these products. / Devido a ausência de uma formulação intracanal totalmente eficaz, é necessária a pesquisa de novas medicações a partir de plantas medicinais. Nesse caso a Ximenia americana L., planta da catinga, amplamente utilizada pela medicina tradicional como antibacteriano, pode ser indicada para desenvolvimento de formulações intracanais. Todavia, não existe uma padronização do seu extrato pela indústria farmacêutica, no que diz respeito a estudos de préformulação e padronização de técnicas analíticas para determinação de sua segurança, eficácia e qualidade. Nesse contexto, com esse estudo pretendeu desenvolver a partir de X. americana L. uma pasta intracanal, com atividade antimicrobiana, aplicando parâmetros de validação de processo para os ensaios de potencia microbiológica, doseamento do componente químico majoritário, estudos toxicológicos e de compatibilidade fármaco excipiente. Foram obtidos dois tipos de extratos a partir da casca de X. americana L, hidroalcóolicos que posteriormente foi selecionado nebulizado em spray dryer e extrato etánolico que foi concentrado em evaporador rotativo. Para determinação, da atividade antimicrobiana, utilizou os extratos hidroalcólicos aplicando a técnica de difusão ágar/cilindros. Os ensaios toxicológicos consistiram na determinação da toxicidade aguda e citotoxicidade. A análise fitoquímica foi baseada na determinação quantitativa de polifenóis totais, flavonoides totais, taninos condensados e saponinas totais. O composto químico majoritário foi identificado como ácido gálico através da cromatografia líquida de alta eficiência, assim como seu doseamento, o qual foi validado de acordo com os compêndios oficiais. Foi realizado o processo de validação do doseamento microbiológico da X. americana em relação ao padrão (ácido gálico). O estudo de compatibilidade fármaco/excipiente foi realizado aplicando técnicas termo analíticas e espectroscopia na região do infravermelho. X. americana L, apresentou atividade contra Staphilococcus aureus, Enterococcus faecalis, Streptococcus oralis e Klebsiella pneumoniae. Quanto a segurança biológica, essa planta não apresentou toxicidade nos ensaios analisados. A análise fitoquímica demonstrou níveis aceitáveis de concentrações de metábólitos secundários. O marcador foi identificado e quantificado na concentração de 12µg/mL. Quanto ao doseamento microbiológico, esse apresentou linearidade, precisão exatidão, limites de detecção e quantificação e robustez dentro das especificações. Quanto ao estudo de compatibilidade os excipientes que foram incompatíveis nas técnicas termoanalíticas, na espectroscopia essas incompatibilidades não foram tão intensas, no que respeito a supressão de grupos funcionais dos excipientes e do extrato seco. Assim estudos que mostrem o desenvolvimento de um medicamento fitoterápico, bem como a caracterização e padronização do extrato de X. americana L\ são importantes, devido falta de metodologia oficial que comprove a qualidade, segurança e eficácia de destes produtos.

Os processos fibrogênicos, ativados por mecanismos como estresse oxidativo, podem levar a um quadro de cirrose hepática, que representa uma das principais causas de morte no ocidente. Entretanto, em alguns estudos, substâncias fenólicas, como o Ácido Gálico (AG), demonstraram inibir e até regredir esses processos. O objetivo do presente estudo foi investigar os efeitos do composto fenólico AG no processo fibrogênico hepático murino. Os mesmos foram avaliados tanto na fase de progressão da fibrose, como na cirrose hepática estabelecida pela administração crônica de tetracloreto de carbono em camundongos C57. Para isso foram realizadas análises histológicas, imuno-histoquímicas, PCR e Western-bloting, estimando-se fatores relacionados à fibrogênese e mediadores inflamatórios associados. Observou-se uma diminuição importante na percentagem de áreas coradas pelo Sirius red, ou seja, redução na percentagem de fibrose nos grupos tratados com AG, tanto durante a prevenção (p<0,05), quanto na regressão da cirrose (p<0,05). Esta melhora foi acompanhada de redução no número de células marcadas pela SMA nos grupos tratados (p<0,05). Estes mesmos parâmetros foram confirmados através da análise genômica para colágeno, assim como pelo TIMP e pelo TGF 1; e proteômica para NFB e p38 MAPK. Os achados do presente estudo demonstraram o efeito do AG sobre a prevenção e reversão do processo fibrogênico hepático. Os principais mecanismos deste processo envolvem atividades anti-inflamatórias via TGF-1 e p38 MAPK, principalmente durante a indução de fibrose; assim como restrição da capacidade anti-apoptótica do NFB sobre as células estreladas hepáticas (CEH) na cirrose já estabelecida. / The fibrogenic processes activate by mechanisms such as oxidative stress can lead to a picture of liver cirrhosis, which represents a major cause of death in West. However, in some studies, phenolic substances, such as Gallic Acid (GA) shown to inhibit and even regress theses processes. The aim of this study was to investigate the effects of the phenolic compound GA in murine liver fibrogenic process. They were evaluated both in progression of fibrosis and in liver cirrhosis established by administration carbon tetrachloride im mice C57. For this, was performed histological, immunohistochemical, PCR and Western blotting analysis, estimating factors related to fibrogenesis and inflammatory mediators associated. There was a significant decrease of area stained by Sirius Red, which means reduction in the percentage of fibrosis in the groups treated with GA. Both for prevention (p<0,05) and for the regression of the cirrhosis (p<0,05). This improvement was accompanied by a reduction in the number of cells marked by SMA in the treated groups (p<0,05). These parameters was confirmed by genomic analysis for collagen, as well as by TIMP 1 and TGF 1, and proteomics for p38 MPK and NFkB. The findings of this study demonstrade the effect of GA in the prevention and of liver fibrogenic process. The main mechanisms of this process involves anti-inflammatory activity via TGF 1 and p38 MAPK, especially during induction of fibrosis, as well as restriction of antiapoptotic capacity of NFkB on the CEH in established cirrhosis.

Potato peel, a waste generated from potato processing is a disposal problem. But, it is a good source of phenolic compounds, sugars, and glycoalkaloids. This study examines the subcritical water extraction of phenolics, glycoalkaloids and sugars from potato peel and compares it to conventional solvent extraction. Experiments were conducted in a batch stainless steel reactor at 6 MPa, 2 mL/min and 100 to 240C for 30-120 min. The results revealed that highest recoveries of phenolic compounds (81.23 mg/100 g; fw) and sugars (75 mg/g; fw) were obtained using subcritical water at 180C and 30 min and at 160C and 120 min, respectively. Low content of glycoalkaloids (1.19 mg/100 g, fw) was obtained using subcritical water. The yields of phenolics and sugars using subcritical water were 40 and 45% higher than using a conventional solvent extraction method. Therefore, subcritical water might be a good substitute to organic solvents such as methanol and ethanol to obtain functional ingredients from potato peel. / Food Science and Technology

Gallic acid esters (GAE) of varying alkyl chain length were used to determine how antioxidant physical location and partitioning influence hemoglobin-catalyzed lipid oxidation. Specific GAE used were propyl gallate (PG), octyl gallate (OG), and lauryl gallate (LG). GAE partitioning experiments were performed with either isolated cod muscle membranes or washed cod muscle, which primarily contain polar membrane lipids and myofibrillar proteins. Canola oil was used in some experiments to determine how neutral lipids impact partitioning behavior. GAE distribution was determined spectrophotometrically in the recovered membranes, aqueous phase, and oil layer after employing differential centrifugation. Oxidation was monitored by measuring thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides development.When GAE were added to the membrane suspensions, significant differences (p < 0.05) in GAE partitioning were observed in the aqueous phase and membrane sediment, where increases in GAE alkyl chain length corresponded with a decrease in aqueous phase concentrations and increases in the membranes. GAE partitioning in the oil fraction did not show significant differences. Also, increases in GAE alkyl chain correlated with increases in GAE membrane detection when GAE were added to the washed fish muscle (p < 0.05).Adding GAE to the washed cod muscle before the canola oil was the most effective sequence of addition for extending the storage time before lipid oxidation was detected. Among the three GAE tested, PG showed the greatest inhibition against lipid oxidation. The effectiveness of the GAE in the washed cod-canola oil system follows the order, PG > OG > LG, which corresponds with decreasing hydrophobicity.The conclusions of this study are twofold. First, GAE partitioning into the muscle membranes was not the primary factor for delaying the onset of lipid oxidation. Rather, solubility in the aqueous phase showed the greatest impact on extending storage time. Secondly, the order in which GAE and canola oil were added to the washed cod (WC) muscle system influenced hemoglobin-catalyzed lipid oxidation behavior. Adding GAE before the neutral oil may have allowed the GAE to partition more easily into the polar regions of the washed muscle, which in turn provided the most effective protection against oxidation.

The aim of this study was to analyze the effect of hydrogen peroxide and selected phenolic compounds on growth and catalase production of Aspergillus fumigatus. As a result of growing A. fumigatus at different temperatures it was observed that, growth and catalase production of this species were highest at 37 &deg / C. Catalase production was highest in the presence of 1 mM H2O2, yielding a significant 3 fold increase with respect to the control. Biomass was also increased by 1,44 fold with respect to the control sample. H2O2 increased catalase production possibly by inducing oxidative stress as biomass production significantly increased after the depletion of H2O2. Both gallic acid and trans-resveratrol significantly enhanced biomass generation of A. fumigatus (1,17 fold increase at 10 mM gallic acid and 1,45 fold increase at 3 mM resveratrol with respect to controls) and decreased extracellular catalase production (4,33 fold at 25 mM gallic acid and 16,7 fold decrease at 3 mM resveratrol with respect to controls) especially in the first 5 or 6 days of the cultivation where the anti-oxidant activity of the compounds were possibly at their maximum. A sudden and significant rise was observed in extracellular catalase activity between 5th and 7th days of the cultivation in phenolic compound applied samples, possibly owing to the depletion of the antioxidant activity of gallic acid and resveratrol followed by fungal cells&rsquo / response to a sudden increase of oxidative stress by boosting catalase production.

No description available.

Thesis (M.Sc.) --Memorial University of Newfoundland, 1987. / Typescript. Bibliography: leaves 113-122. Also available online.

No description available.

Orientador: Maria José Soares Mendes Giannini / Banca: Luis Octávio Regasini / Banca: Eduardo Bagagli / Resumo: Paracoccidioides brasiliensis e P. lutzii são fungos dimórficos, agentes etiológicos da paracoccidioidomicose, que é uma micose humana sistêmica geograficamente confinada na América Latina. Vários antifúngicos podem ser utilizados para o tratamento dessa doença, tais como anfotericina B, sulfamídicos e azólicos (itraconazol) e de maneira geral seu uso é prolongado. As limitações frequentes dos antifúngicos e o aumento na incidência das infecções fúngicas sistêmicas têm ressaltado a necessidade da descoberta e do desenvolvimento de novos fármacos. O objetivo deste estudo foi comparar a atividade antifúngica de anfotericina B, itraconazol e galatos de alquila anti-complexo de Paracoccidioides por métodos fenotípicos e proteômicos. Para tanto foi padronizado o teste de sensibilidade para selecionar o galato de maior potência, utilizando o documento M27-A2 (2002), modificado pela adição de Alamar Blue. Adicionalmente, análises proteômicas foram realizadas antes e após tratamento com o antifúngico selecionado para verificar o perfil das possíveis proteínas-alvo. A atividade antifúngica foi estudada contra isolados de P. brasiliensis (S1, S2 e PS3) e P. lutzii, (Pb01-like), e depois o teste foi estendido para mais seis isolados. O valor da CIM do ácido gálico variou de 31,25 a 0,250 mg/L para todos os isolados. Os galatos mostraram valores de CIM entre 16 a 0,004 mg/L. O menor valor de CIM foi observado para seis galatos que possuem uma substituição por uma cadeia relativamente longa de carbonos. O perfil proteico dos isolados Pl01 e Pb18 foi estudado por eletroforese 2D após contato com anfotericina B , itraconazol e o galato de decila (todos a uma concentração de 0,125 mg/L. Mais de 130 spots para ambos os fungos foram observados e a maioria destas proteínas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Paracoccidioides brasiliensis and P. lutzii are dimorphic fungi, etiological agents of paracoccidioidomycosis, which is a systemic human mycosis geographically restricted to Latin America. Various antifungal agents may be used to treat this disease, such as amphotericin B, sulfamidic agents and itraconazole, and these drugs are used in long-term therapies. The limitations of antifungals and increased incidence of systemic fungal infections has underscored the need for discovery and development of new drugs. The objective of this study was to compare the antifungal activity of amphotericin B, itraconazole and alkyl gallates anti-Paracoccidioides complex by phenotypic and proteomic methods. Thus, the susceptibility test was applied to select the most potent gallate, using the document M27-A2 (2002), modified by the addition of Alamar Blue. Finally, proteomic analyses was developed before and after the treatment with the antifungal agent selected, to study the protein profile after this treatment. The antifungal activity was evaluated against isolates of P. brasiliensis (S1, S2 and PS3) and P. lutzii (PB01-like), and after, the test has been extended to six isolates. The MIC values of gallic acid varied from 31.25 to 0.250 mg/L for all isolates. The gallates showed MIC values ranging from 16 to 0,004 mg/L. The lowest MIC value was observed for six gallates bearing a substitution for a long side chain. The protein profile of isolates Pb18 and Pl01 was studied by 2D electrophoresis after contact with amphotericin B, itraconazole and decyl gallate, all in the concentration of (0.125 mg/L ). More than 130 spots for both species were observed, and the most of these proteins... (Complete abstract click electronic access below) / Mestre

Orientador: Míriam Dupas Hubinger / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-24T20:09:52Z (GMT). No. of bitstreams: 1 Consoli_Larissa_M.pdf: 32030703 bytes, checksum: 03d005ea2ebe3bbcf9a246d82a8d00a2 (MD5) Previous issue date: 2014 / Resumo: Os compostos fenólicos são conhecidos por suas propriedades antioxidantes, mas podem apresentar susceptibilidade a fatores como oxigênio e luz, perdendo estas propriedades. A microencapsulação pode ser uma alternativa para a proteção destes compostos. A técnica de spray chilling apresenta vantagens como custo relativamente baixo e possibilidade de ampliação de escala. Este trabalho teve como objetivo a aplicação da tecnologia spray chilling à microencapsulação de compostos fenólicos, utilizando ácido gálico como composto fenólico modelo. Misturas de óleo de soja (OS) e óleo de soja totalmente hidrogenado (OSTH) (com proporções de 20 a 90 % de OSTH) foram avaliadas como materiais de parede. Os lipídios foram caracterizados quanto à composição em ácidos graxos, comportamento térmico por calorimetria de varredura diferencial (DSC) e isoterma de cristalização. Avaliou-se a capacidade de formação de partículas de cada mistura através da atomização em spray chilling. O ácido gálico (solução aquosa a 6 % g/g e 60 °C) foi disperso nas misturas lipídicas com o emulsificante PGPR (polirricinoleato de poliglicerol) para formação de emulsões, preparadas com 4 % de emulsificante (em relação à massa lipídica) e 4 minutos de agitação a 9.500 rpm. As micropartículas foram produzidas variando-se a proporção OSTH : OS (60:40, 70:30, 80:20 e 90:10) e a razão MP:MR (material de parede e material de recheio ¿ 70:30 e 80:20), com os seguintes parâmetros: diâmetro do bico atomizador de 0,7 mm, vazão do ar de resfriamento e do ar no bico atomizador, de 35.000 L/h e 667 L/h, respectivamente. A vazão de alimentação da emulsão foi de 0,530 L/h. Foram obtidas micropartículas com eficiências de encapsulação variando de 54,14 ± 2,82 (%) até 101,83 ± 6,74 (%). Maiores proporções de OSTH na mistura lipídica e a menor razão MP : MR influenciaram no aumento da eficiência de encapsulação. Os diâmetros médios variaram de 23,91 ± 1,60 µm a 35,98 ± 2,17 µm e apresentarem oscilação pequena em função das variáveis. A morfologia mostrou partículas de forma esférica e superfície lisa, com presença de cristais e alguns aglomerados de partículas menores. Avaliou-se a estabilidade de duas formulações por 28 dias armazenadas a 5 e 25 °C. A estocagem refrigerada conferiu melhores características de liberação do recheio no meio aquoso e evitou a formação de aglomerados de partículas / Abstract: Phenolic compounds are known for their antioxidant properties, but they may exhibit susceptibility to factors such as oxygen and light, which may cause them to lose these properties. Microencapsulation can be an alternative for the protection of these compounds. The spray chilling technique presents advantages such as relatively low cost and the possibility of scaling-up. This work presented aimed the implementation of the spray chilling technique for the microencapsulation of phenolic compounds, using gallic acid as a model phenolic compound. Blends of soybean oil (SO) with fully hydrogenated soybean oil (FHSO) (in proportions from 20 up to 90% of FHSO) were assessed as wall materials. Lipids were characterized for fatty acid composition, thermal behavior by differential scanning calorimetry (DSC) and isothermal crystallization. The particle-forming ability of each blend was evaluated by atomization in spray chilling. Gallic acid (aqueous solution at 6 % wt/wt - 60 °C) was dispersed in the lipid blends with the emulsifier PGPR (polyglycerol polyricinoleate) for forming emulsions, which were prepared with 4 % of emulsifier (relative to mass of lipid) and stirred for 4 minutes at 9500 rpm. Production of microparticles were made varying the proportion FHSO : OS (60:40 , 70:30 , 80:20 and 90:10) and the ratio WM : CM (wall material to core material - 70:30 and 80:20 ), with the following parameters: diameter of the atomizer nozzle 0.7 mm, cooling air flow and atomizing air flow rates were, respectively, 35,000 L/h and 667 L/h. The feed flow rate of the emulsion was 0.530 L/h. Encapsulation efficiencies of microparticles ranged from 54.14 ± 2.82 (%) to 101.83 ± 6.74 (%). Higher proportions of FHSO in the lipid mixture and the smallest ratio WM : CM led to greater encapsulation efficiencies. The average diameters ranged from 23.91 ± 1.60 µm to 35.98 ± 2.17 µm and presented small variation in function of the variables. The morphology showed particles of spherical shape and smooth surface with some crystals and agglomerates of smaller particles. The stability of two formulations was evaluated over 28 days under different storage temperatures (5 and 25 °C). Storage under refrigeration gave the best release characteristics in aqueous media and prevented the formation of particle agglomerates / Mestrado / Engenharia de Alimentos / Mestra em Engenharia de Alimentos