As tetraciclinas são encontradas no mercado sob várias formas farmacêuticas, sendo provenientes de diversos laboratórios farmacêuticos. Com o objetivo de avaliar a qualidade destes medicamentos, foram realizados os ensaios de dissolução in vitro e determinação quantitativa. Um total de 38 amostras de cápsulas de cloridrato de tetraciclina, fosfato de tetraciclina e cloridrato de oxitetraciclina e drágea de cloridrato de doxiciclina, englobando 12 fabricantes, foram analisadas. A dissolução do princípio ativo foi determinada para todas as amostras, conforme o método recomendado pela USP XXIII. Das amostras, duas foram reprovadas e outras quatro foram aprovadas após o reteste. A variação dos valores individuais obtidos no ensaio de dissolução para cada amostra, foi significativa, apresentando coeficiente de variação de até 14,2 %. A determinação quantitativa através do método microbiológico turbidimétrico empregando Staphylococcus aureus ATCC 29737, resultou em duas amostras de um mesmo fabricante com potência muito abaixo do limite especificado de 90 a 125 % do valor rotulado, com 55.5 e 68,7 %. Estudo comparativo desta metodologia com o método de cromatografia líquida de alta eficiência (CLAE) foi realizado. Para isto, o método da USP XXIII foi escolhida após o ensaio preliminar, seguido de determinação dos parâmetros de validação e adequação do método. O sistema cromatográfico estabelecido consistiu de coluna de fase reversa SYMMETRYTM C8 e fase móvel composta de oxalato de amônio 0,09 M, dimetilformamida e fosfato dibásico de amônio 0.18 M (64:32:4.7) com pH entre 7,6 e 7.7. Os resultados para determinação de cloridrato de tetraciclina confirmaram os valores obtidos no ensaio microbiológico, sendo reprovadas duas amostras. O teor máximo encontrado de 4-epianidrotetraciclina foi de 0,5 %, abaixo do limite de 3 % especificado na USP XXIII. Na comparação entre os dois métodos, foram observados resultados sempre superiores para o método microbiológico. A análise estatística destes resultados mostrou diferença significativa entre as médias das determinações obtidas a partir de cada método. / Tetracyclines are avaiable under several pharmaceutical forms and manufactured by different laboratories. Aiming at the evalution of the quality of these medicines, assays of in vitro dissolution and quantitative determination have been performed in 38 samples of tetracycline hydrochloride and phosphate and oxytetracycline hydrochloride capsules and docycycline hydrochloride coated tablet taken from 12 manufactures. The range of dissolution of the substance was determined in all the samples, according to the method recommended by USP XXIII. On the whole, only two of samples were rejected and all the others approved without restrictions, except four of them, wich required a retest. The evaluation of the individual values obtained in the assay of dissolution in each sample was significant, with a variation coefficient of up to 14.2%. The quantitative determination through the turbidimetric microbiological method employing Staphylococcus aureus ATCC 29737, resulted in two samples of tetracycline hydrochloride from the same manufatures with potency of 55.5 % and 68.7 % below the specified limit from 90 % to 125 % the labeled value. A comparative study of this method and the HPLC one was then performed. The USP XXIII method was chosen after a preliminary assay, followed by the determination of its validation parameters and system suitability. The established chromatographic method employed reversed phase column SYMMETRYTM C8 (octylsilane chemically bounded to totally porous sílica particles) and mobile phase consisting of ammonium oxalate 0.09 M, dimethyformamide and dibasic ammonium phosphate 0.18 M (63.9:32:4.7) adjusted to pH 7.6-7.7. The results confirmed the values obtained in the microbiological assay. When this method (HPLC) was used for the determination of 4-epianidrotetracycline, a maximum of 0.5 % was found, below the limit of 3% specified in the USP XXIII. The comparison between both methods reavealed constant superior results in the microbiological one, and the difference between the averages of the determinations from the methods was meaningful.

Made available in DSpace on 2015-04-22T22:02:15Z (GMT). No. of bitstreams: 1 Edinilze Souza Coelho Oliveira.pdf: 4961035 bytes, checksum: f6de1b94d1c9a5c50a72d78882119b88 (MD5) Previous issue date: 2012-09-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Leishmaniasis is considered by the World Health Organization as one of the most severe infections, due to have high capacity to produce deformities. The existing drugs are highly toxic and the parasites have been showed resistance to these drugs. Scientific researches have been proven the antiparasitic potential of extracts and compounds isolated from plant species. The subject of this work is to obtain essential oils from leaves of three species of from Myrtaceae: Eugenia patrisii, Marlierea umbraticola and Myrciaria floribunda, two species from Myristicaceae: Virola mollissima and V. theiodora, one specie from Annonaceae: Bocageopsis multiflora and one specie from Lauraceae: Endlicheria bracteolata, collected at the Adolpho Ducke Forest Reserve, Manaus, AM. The collections were performed in two periods: winter (April) and summer (September). The analysis of essential oils of E. patrisii, M. floribunda, B. multiflora and V. mollissima by GC-MS showed a high percentageof sesquiterpenes, while oils M. umbraticola and V. theiodora presented the monoterpenes as main constituents. The essential oil of the fresh leaves from E. bracteolata presented a differential when extracted in the month of April. There was observed the precipitate during the extraction and when analyzed by GC-MS showed a chromatographic profile of about 73.7% oxygenated sesquiterpenes. However, the oil of the dry season showed the hydrocarbons sesquiterpene as major constituents. The solid material obtained from E. bracteolata was purified, and guaiol was identified by MS, NMR and comparison with the literature data. The study with the heartwood from V. mollissima led to obtain a precipitate of the hexane extract and isolation of neolignans carinatin and dehydrodieugenol. Concerning the pharmacological tests, essential oils and extracts of low polarity were tested on the promastigotes of Leishmania amazonensis. In this context, the oil V. mollissima showed highr activity (IC50 of 19.7g/mL). The neolignan carinatina showed lower activity with value IC50 of 53.9g/mL. The essential oils from B. multiflora and M. umbraticola were the most active with IC50 of 14.8 and 21.1g/mL, respectively. The extracts that showed highest activity on promastigotes from L. amazonensis were subjected to the cytotoxicity analysis in non-infected macrophages, and oil from V. mollissima was the most toxic with IC50 of 17.16g/mL 10 compared to standard pentamidine (IC50 = 24.40 g/mL), while the oil from B. multiflora showed less toxicity with IC50 = 42.71g/mL. When evaluated against brine shrimp Artemia salina, all the oils exhibited high toxicity compared to standard lapachol (LC50 = 10.47g/mL), being the essential oil from E. bracteolata the most toxic with LC50 of 0.53g/mL. The antioxidant activity evaluation against the radical free DPPH below 28% of activity to the essential oils. In contrast, the neolignan deidrodieugenol and precipitate obtained from V. mollissima, exhibit high antioxidant activity with IC50=10.68 and IC50=6.87g/mL, respectively. / A leishmaniose é considerada pela Organização Mundial de Saúde como uma das mais graves infecções existentes, por causa da sua alta capacidade de produzir deformidades. Os medicamentos existentes são de elevada toxicidade e o parasita tem apresentado resistência a esses medicamentos. Pesquisas científicas tem comprovado o potencial antiparasitário de extratos e substâncias isoladas de espécies vegetais. Este trabalho teve como objetivo principal a obtenção de óleos essenciais das folhas de três espécies da família Myrtaceae: Eugenia patrisii, Marlierea umbraticola e Myrciaria floribunda, duas espécies da família Myristicaceae: Virola mollissima e V. theiodora, uma espécie da família Annonaceae: Bocageopsis multiflora e uma espécie da família Lauraceae: Endlicheria bracteolata, ocorrentes na Reserva Florestal Adolpho Ducke, Manaus, AM. As coletas foram realizadas em dois períodos correspondentes ao inverno (abril) e verão (setembro). As análises dos óleos essenciais de E. patrisii, M. floribunda, B. multiflora e V. mollissima por CG-EM evidenciaram alta porcentagem de sesquiterpenos, enquanto que os óleos de M. umbraticola e V. theiodora apresentaram monoterpenos como constituintes majoritários. Já o óleo essencial das folhas frescas de E. bracteolata apresentou um diferencial quando extraído no mês de abril. Um precipitado foi observado durante a extração e quando analisado por CG-EM apresentou um perfil cromatográfico com cerca de 73,7% de sesquiterpenos oxigenados. Entretanto, o óleo da estação seca apresentou sesquiterpenos hidrocarbonetos como constituintes principais. O material sólido obtido de E. bracteolata foi purificado, e o guaiol foi identificado por EM, RMN e comparação com dados descritos da literatura. O estudo com o cerne de V. mollissima levou a obtenção de um precipitado do extrato hexano e ao isolamento das neolignanas carinatina e deidrodieugenol. Concernente aos ensaios farmacológicos, os óleos essenciais e extratos de baixa polaridade foram testados frente às formas promastigotas de Leishmania amazonensis. Nesse contexto, o óleo de V. mollissima exibe maior atividade (CI50 de 19,7 g/mL) e a neolignana carinatina apresenta menor atividade com valor de CI50 de 53,9 g/mL. Em relação aos óleos das demais espécies, os 8 óleos essenciais de B. multiflora e de M. umbraticola foram os mais ativos com CI50 de 14,8 e 21,1 g/mL, respectivamente. Os extratos que demonstraram maior atividade sobre as formas promastigotas de L. amazonensis foram submetidos ao ensaio de citotoxicidade em macrófagos não parasitados, sendo o óleo de V. mollissima o mais tóxico com CI50 de 17,16 g/mL em comparação ao padrão pentamidina (CI50 = 24,40 g/mL), enquanto que o óleo de B. multiflora apresentou menos toxicidade com CI50 de 42,71g/mL. Quando avaliados frente ao microcrustáceo Artemia salina, todos os óleos apresentaram elevada toxicidade em relação ao padrão lapachol (CL50 =10,47g/mL), sendo o óleo essencial de E. bracteolata o mais tóxico com CL50 de 0,53g/mL. A avaliação da atividade antioxidante frente ao radical livre DPPH demonstrou que os óleos apresentaram atividade abaixo de 28%. Em contrapartida, a neolignana deidrodieugenol e o precipitado obtido de V. mollissima, apresentam atividade bastante pronunciada com CI50=10,68 e CI50=6,87 g/mL, respectivamente. Palavras-chave: Óleos essenciais, análise cromatográfica, leishmaniose,

O objetivo deste trabalho de pesquisa foi de fazer a modelagem por meio de sistemas de inferência Fuzzy da análise da concentração dos gases dissolvidos no óleo mineral isolante e desta forma diagnosticar defeitos elétricos internos em transformadores de Potência. Assim sendo o sistema proposto deve fornecer respostas que auxiliem no diagnóstico de falhas e avarias nos interiores dos transformadores e no processo de tomada de decisões no acompanhamento da evolução destas falhas de forma a aumentar a confiabilidade em relação à utilização dos métodos individualmente. O sistema desenvolvido baseou-se na pesquisa acadêmica de normas e técnicas mais utilizadas na literatura que relacionam o gás dissolvido no óleo mineral isolante com a falha. O sistema proposto foi validado por meio de dados reais de dois transformadores pilotos e vários sistemas Fuzzy foram construídos, cada um especialista em um determinado método. Os resultados encontrados mostraram-se compatíveis com aqueles obtidos pelos métodos convencionais comprovando que a ferramenta pode ser utilizada como suporte para uma análise rápida e confiável do estado do óleo isolante dos transformadores. / The objective of this research was to model by analyzing the fuzzy inference systems the concentration of gases dissolved in the insulating oil and diagnosing thereby internal defects in electrical power transformers. Therefore the proposed system should provide answers that help in the diagnosis of faults and malfunctions in the interiors of the transformers and in the decision-making process in monitoring the evolution of these failures in order to increase the reliability regarding the use of the methods individually. The system developed was based on academic research standards and techniques commonly used in the literature relating the gas dissolved in the insulating oil with failure. The proposed system was validated by real data of two pilots transformers and various Fuzzy systems were built, each an expert in a particular method. The results were compatible with those obtained by conventional methods proving that the tool can be used as support for quick and reliable analysis of the insulating oil condition of transformers.

Adsorption separation processes are extremely important to the chemical industry, especially in the manufacturing of food, pharmaceutical, and fine chemical products. This work addresses three main topics: first, systematic decision-making between rival gas phase adsorption processes for the same separation problem; second, process development for liquid phase simulated moving bed chromatography (SMB); third, accelerated startup for SMB units. All of the work in this thesis uses model-based optimization to answer complicated questions about process selection, process development, and control of transient operation. It is shown in this thesis that there is a trade-off between productivity and product recovery in the gaseous separation of enantiomers using SMB and pressure swing adsorption (PSA). These processes are considered as rivals for the same separation problem and it is found that each process has a particular advantage that may be exploited depending on the production goals and economics. The processes are compared on a fair basis of equal capitol investment and the same multi-objective optimization problem is solved with equal constraints on the operating parameters. Secondly, this thesis demonstrates by experiment a systematic algorithm for SMB process development that utilizes dynamic optimization, transient experimental data, and parameter estimation to arrive at optimal operating conditions for a new separation problem in a matter of hours. Comparatively, the conventional process development for SMB relies on careful system characterization using single-column experiments, and manual tuning of operating parameters, that may take days and weeks. The optimal operating conditions that are found by this new method ensure both high purity constraints and optimal productivity are satisfied. The proposed algorithm proceeds until the SMB process is optimized without manual tuning. In some case studies, it is shown with both linear and nonlinear isotherm systems that the optimal performance can be reached in only two changes of operating conditions following the proposed algorithm. Finally, it is shown experimentally that the startup time for a real SMB unit is significantly reduced by solving model-based startup optimization problems using the SMB model developed from the proposed algorithm. The startup acceleration with purity constraints is shown to be successful at reducing the startup time by about 44%, and it is confirmed that the product purities are maintained during the operation. Significant cost savings in terms of decreased processing time and increased average product concentration can be attained using a relatively simple startup acceleration strategy.

Sphingolipids are found in essentially all animals, plants and fungi, and some prokaryotic organisms and viruses. Sphingolipids function as structural components of membranes, lipoproteins, and as cell signaling modulators and mediators. To complicate matters further, sphingolipids often vary in type in different regions of tissues, and even in single cells, the subcellular localization of sphingolipids and their metabolic enzymes, transport proteins and targets may influence their functions. It is important to study sphingolipids spatial distribution within living organisms to understand how sphingolipids are involved in complex biochemical processes. As part of this thesis, procedures were optimized for the use of matrix assisted laser desorption/ionization (MALDI) tissue mass spectrometry (TIMS) to visualize the location of several types of lipids including sulfatides (ST), gangliosides and phosphoglycerolipids in brains from a mouse model for Tay-Sachs/Sandhoff disease. MALDI-TIMS was next applied to human ovarian carcinoma tissue to detect sulfatide location and established that ST are associated specifically with the regions of the ovarian tissue that bear the carcinoma. Electrospray ionization tandem mass spectrometry (ESI-MS-MS) was also used to confirm that ST and galactosylceramide (GalCer) are elevated in ovarian cancer. Gene expression data using tumor cells collected using laser capture microdissection revealed greater expression of mRNAs for GalCer synthase, GalCer sulfotransferase (Gal3ST1) and other enzymes of ST biosynthesis in epithelial ovarian carcinoma cells. This is a unique combination of two complementary, profiling technologies--mass spectrometry (metabolomic approach) with analysis of gene expression to study complex cancer pathology. The next study focused on the subcellular location of sphingolipids. In comparison with wild type Hek293 cells, a Hek293 cell line stably overexpressing serine palmitoyltransferase (SPT1/2 cells) was found to have elevated amounts of all subspecies of ceramide (Cer), but produces disproportionately higher amounts of C18-Cer and GalCer. Since Cer is known to inhibit protein ER/Golgi trafficking, these studies found that the higher production of Cer caused impairment of ER/Golgi trafficking of Ceramide synthase 1 (CerS1), thus increased C18-Cer. In addition, since GalCer is only synthesized in the lumen of the ER, this impairement of ER/Golgi trafficking also gave GalCer synthase access to its substrate and increased GalCer biosynthesis. These studies illustrate the complexity of sphingolipid biology and the usefulness of multiple tools to understand sphingolipid complex biological processes.

D. Tech. Chemistry. / Aims to isolate and characterise mesembrine-type alkaloids from S. tortuosum for use as reference standards ; develop and validate analytical methods for the accurate determination of mesembrine-type alkaloids in S. tortuosum samples and commercial products for quality control purposes ; investigate inter-species variation of alkaloids in endemic Sceletium species ; establish the variation of mesembrine-type alkaloids within and between different populations of S. tortuosum specimens and hence identify various chemotypes ; determine the variations of the target alkaloids in S. tortuosum commercial products purchased from various suppliers ; determine the mesembrine-type alkaloid content of the combustion products from S. tortuosum; and to evaluate the in vitro permeation of the alkaloids across oral and intestinal mucosa.

This thesis describes the characterization of ceramide (Cer) biosynthesis by mammalian cells. The possibility that Cer undergo developmental changes was explored using mouse embryonic stem cells versus embryoid bodies by analysis of the Cer subspecies by liquid chromatography, electrospray ionization-tandem mass spectrometry (LC ESI-MS/MS) and of the transcript levels for enzymes involved in Cer biosynthesis by qRT-PCR. Cer of embroid bodies had higher proportions of very-long-chain fatty acids, which correlated with the relative expression of mRNA for the respective Cer synthases (CerS) and fatty acyl-CoA elongases, as well as changes in the fatty acyl-CoA's of the cells. Therefore, it is clear that Cer subspecies change during embryogenesis, possibly for functionally important reasons. One CerS isoform, CerS2, was studied further because it has the broadest tissue distribution and a remarkable fatty acyl-CoA specificity, utilizing longer acyl-chain CoAs (C20-C26) in vitro. The fatty acid chain selectivity was refined by analysis of the Cer from livers from CerS2 null mice, which displayed very little Cer with fatty acyl chains with 24 + 2 carbons. Another interesting structural variation was discovered in studies of cells treated with fumonisin B1 (FB1), which inhibits CerS. Under these conditions, cells in culture and animals accumulate substantial amounts of a novel sphingoid base that was identified as 1-deoxysphinganine. This compound arises from utilization of L-alanine instead of L-serine by serine palmitoyltransferase (SPT) based on the inability of LYB cells, which lack SPT, to make 1-deoxysphinganine. In the absence of FB1, 1-deoxysphinganine is primarily acylated to 1-deoxydihydroceramides. These are an underappreciated category of bioactive sphingoid bases and "ceramides" that might play important roles in cell regulation and disease. In summary, cells contain a wide variety of Cer subspecies that are determined by changes in expression of CerS, enzymes that produce co-substrates (such as fatty acyl-CoAs), and the types of amino acids utilized by SPT, the initial enzyme of de novo sphingolipid biosynthesis. One can envision how these changes might impact membranes structure as well as signaling by this family of highly bioactive compounds.

Thesis (Ph.D.) -- University of Western Sydney, Hawkesbury, 1998. / "A thesis presented to the University of Western Sydney for the degree of Doctor of Philosophy, September, 1998" Bibliography: leaves 193 - 219.

Mémoire (M.P.Aquat.)--Université du Québec à Chicoutimi, 1990. / Document électronique également accessible en format PDF. CaQCU

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Atualmente têm-se verificado um aumento acentuado na demanda de mercado em relação a óleos vegetais das mais diversas fontes naturais. Os óleos vegetais são extraídos na sua maioria das sementes de plantas, formados por ésteres de glicerina e uma mistura de ácidos graxos, esteróis, tocoferóis e resíduos minerais. Medições rápidas e não destrutivas dos parâmetros relacionados com a qualidade de alimentos estão avançando devido ao progresso da espectroscopia, pois permitem aos pesquisadores obter informações importantes dos componentes químicos e físicos dos alimentos. Nesse sentido, a quimiometria colabora para a transformação dos sinais analíticos de amostras complexas em informações úteis, o método quimiométrico empregado nos estudos foi a análise multitabelas (ComDim), cujo objetivo foi avaliar tabelas (ou matrizes) de dados adquiridos para as mesmas amostras (isto é, um conjunto de matrizes de dados com o mesmo número de linhas, mas não necessariamente o mesmo número de variáveis). Com a aplicação do método ComDim foram obtidos gráficos informativos que mostraram a relação entre as amostras e suas variáveis, além de permitir avaliar em qual das tabelas analisadas encontra-se a informação predominante. Como resultado da primeira pesquisa, o método ComDim permitiu realizar um reconhecimento de padrão não supervisionado auxiliando na identificação de semelhanças e diferenças entre as amostras de óleos e azeites de oliva. Para os óleos de arroz foi possível correlacionar as regiões espectrais do UV-Vis e NIR, bem como as análises físico químicas inferindo sobre início e estágios mais avançados das reações de degradação. . / We currently have a marked increase in market demand for vegetable oils from a variety of natural sources. Vegetable oils are extracted mostly from plant seeds, consisting of glycerol esters and a mixture of fatty acids, esters, tocopherols and mineral residues. Fast and non-destructive measurements of food quality data are advancing due to the progress of spectroscopy, for research researchers to obtain important data of the chemical and physical components of food. In this sense, chemometrics collaborates to transform the analytical signals of complex samples into useful information, the chemometric method used in the studies was the multi-table analysis (ComDim), whose objective was to evaluate tables (or matrices) of data acquired for the same samples (that is, a set of data arrays with the same number of rows, but not necessarily the same number of rows). With the application of the ComDim method, informative graphs were obtained that showed the relation between the samples and their variables, besides allowing to evaluate in which of the analyzed tables the predominant information is found. As a result of the first research, the ComDim method allowed the realization of an unsupervised pattern recognition, aiding in the identification of similarities and differences between samples of oils and olive oils. For rice oils it was possible correlates UV-Vis and NIR spectral regions, also physical-chemical analysis and attribute the start and advanced stages for degradation reactions.