Magister Pharmaceuticae - MPharm / Recent scientific findings have highlighted the beneficial roles of polycyclic cage compounds in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Further interest into the chemistry of these compounds is stimulated by their remarkable ability to improve the pharmacokinetics profile of known neuroprotective agents. As potent lipophilic scaffolds, they can be employed to target the brain delivery of desired compounds. Inflammation is a key mediator of neuronal cell's degeneration as activated microglia and other inflammatory mediators propagate oxidative damage and neuronal loss. Epidemiological and clinical evidence suggests that non-steroidal anti-inflammatory drugs (NSAIDs) slow down the progression and onset of neurodegenerative diseases. The beneficial effects of NSAIDs in ND can be attributed to their ability to inhibit cyclooxygenase enzymes thereby halting the biosynthesis of prostaglandins (PG) which are powerful mediators of inflammation. NSAIDs also inhibit the expression of pro- inflammatory genes. Despite their potential neuroprotective activity, NSAIDs are poorly lipophilic due to the presence of polar carboxylic acid groups and will therefore ionise at physiological pH, deterring them from reaching the desired site of action in the central nervous system (CNS).

The Barton Springs salamander (Eurycea sosorum) is a federally endangered species that is endemic to Barton Springs in Austin, Texas. Development within the Barton Springs watershed threatens the continued existence of E. sosorum. A factor that may be contributing to its decline is contamination from polycyclic aromatic hydrocarbons (PAHs). Nearby asphalt parking lots paved with coal-tar and asphalt sealants can be sources of PAHs. Unaltered parent compounds of PAHs can have toxic effects, but oxidation and ultraviolet radiation can create degradation products 100 times more toxic than the parent compounds. The objective of this project was to determine if PAHs are potentially harmful to E. sosorum using two surrogate species. Adult eastern newts (Notophthalmus viridescens) and larval spotted salamanders (Ambystoma maculatum) were exposed to sediments with nominal concentrations of total PAHs that ranged from 0 to 1500 mg/kg under UV (290 - 400 nm) and visible (400 - 700 nm) light to determine concentration/response relationships. No statistically significant mortality occurred under any treatment. Exposure to both coal-tar sealant and UV light resulted in sublethal effects such as decreased righting ability and swimming speed. Difficulty in performing such movements would make it difficult to catch prey and increase susceptibility to predation. Exposure to UV light also resulted in elevated numbers of micronucleated erythrocytes and white blood cells. This study shows that simultaneous exposure to PAHs and UV light result in sublethal effects that could make the population of E. sosorum vulnerable to further decline.

Made available in DSpace on 2014-06-11T19:35:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2000-04-27Bitstream added on 2014-06-13T19:05:07Z : No. of bitstreams: 1 poppi_nr_dr_araiq.pdf: 2732054 bytes, checksum: 0800f7d3640b4b73c285c261aa5734ff (MD5) / município de Campo Grande, MS, com uma população de aproximadamente 600 mil habitantes concentrados na área urbana, todos os anos, entre os meses de julho a novembro, período muito seco, fica encoberto pela fumaça proveniente da queima de biomassa, a qual tem sido apontada como responsável pelo aumento da incidência de casos de doenças respiratórias na população. Neste trabalho, é reportada a composição química de aerossóis, partículas inaláveis (1 μm ≤ dp≤ 15 μm), de emissões do forno utilizado para a produção de carvão vegetal e de 14 amostras de ar da cidade de Campo Grande / MS. O particulado atmosférico foi amostrado de junho a novembro de 1998 no campus da UFMS e as amostras de emissão direta foram coletadas a 1,5 m de um forno construído com tijolos e saibro, similar aos utilizados nas carvoarias da região. Nos dois tipos de amostra, o material particulado foi coletado sobre filtro de Fluorepore em PTFE com 37 mm de diâmetro e as substâncias semivoláteis em tubos do adsorvente XAD-2, utilizando-se amostrador de baixo volume (low-vol). As substâncias foram extraídas com diclorometano/metanol (4:1) em banho ultra-sônico. As análises foram realizadas por CG/EM nos modos SCAN e SIM. A concentração de HPAs na atmosfera próxima ao forno, proveniente da queima de madeira para produção de carvão, foi estimada em 23,6 μg.m-3 de ar para a soma de 15 HPAs, e em 310,1 ng.m-3 para o BaP. A concentração média dos 15 HPAs nas amostras ambientais foi de 21,05 ng.m-3 e a concentração média do BaP de 0,25 ng.m-3... / Campo Grande City (Mato Grosso do Sul State, Brazil) has around 600,000 inhabitants, concentrated in the urban area. Every year, between July and November, the dry season, the city is covered with biomass burning smoke. The biomass burning is result of the vegetal carbon production, agricultural handling, or de-florestation operation into Brazilian Savannah (“cerrado”). The smoke has been indicated as main cause of respiratory disease increasing of the population. In this work it was reported the aerosol composition (1μm ≤ dp≤ 10 μm), from emission of vegetal carbon production and 14 air samples of Campo Grande city. The particulate material was sampled from June until November, 1998 at campus of Federal University of Mato Grosso do Sul (UFMS) while the emission samples were collected at 1.5 m far from an oven made with brick and a mixture of clay and sand, similar to ones used by vegetal carbon producers of region. For both kind of samples, the particulate material was collected with Fuorepore/PTFE filters (37 mm diameter) while volatile fraction was sampled into adsorbent tubes (XAD-2), using low vol sampler. The extracts were obtained by ultrasonic bath using dichloromethane:methanol (4:1) and were analyzed by GC/MS, SCAn and SIM modes. The total HPAs emission of vegetal carbon oven was estimated in 23.6 μg.m-3 and 310 ng.m-3 for benzo(a)pyrene. On the other hand, the city air samples shown concentration (average) of 21,05 ng.m-3 for total HPAs, and 0.25 ng.m-3 for benzo(a) pyrene. HPAs, OXI-HPAs, phenols e Metoxy-phenols were identified...(Complete abstract, click electronic access below)

Made available in DSpace on 2014-12-02T11:16:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-01-17Bitstream added on 2014-12-02T11:21:05Z : No. of bitstreams: 1 000748808_20160131.pdf: 1145880 bytes, checksum: 9fb3124f890c373c2a716642bfa96e7a (MD5) Bitstreams deleted on 2016-02-01T10:15:55Z: 000748808_20160131.pdf,. Added 1 bitstream(s) on 2016-02-01T10:16:45Z : No. of bitstreams: 1 000748808.pdf: 4286658 bytes, checksum: 8f952ac5669d4bfdeb244e9023369477 (MD5) / Os HPA são contaminantes orgânicos formados tanto na queima da palha de cana-de-açúcar quanto de combustível fóssil e por suas características físicoquímicas estão associados ao material particulado fino, podendo assim ser transportado a longas distâncias em um curto espaço de tempo dependendo das condições climáticas. Pelas características de mutagenicidade, carcinogecidade e alteração endócrina são substâncias que tem merecido interesse dos pesquisadores na avaliação da exposição humana por diversas vias, sendo a via alimentar a menos explorada atualmente. Este trabalho teve por objetivo otimizar e validar um método para determinação de HPA em hortaliças e avaliar a presença destas substancias em alface, couve e rúcula , em localidades com e sem a influência da queima de cana-de-açúcar (Araraquara e Itu). O método otimizado e validado neste trabalho envolve extração por banho de ultrassom e detecção por HPLC/FLU, possui valores aceitáveis de LD e LQ de acordo com a União Européia, 0,3 e 0,9 µg kg-1 respectivamente e valores de CV (<11,6%) e recuperação (70~119%), de acordo com os valores preconizados pela ANVISA. Amostras de alface, rúcula e couve cultivados em duas cidades em três diferentes locais, Araraquara (zona rural e zona urbana) e Itu (zona urbana) no período correspondente a safra (agosto de 2012) e entressafra (março 2013) da cana-de-açúcar foram analisadas. As concentrações de HPA encontradas nestas hortaliças situaram-se abaixo dos níveis reportados na literatura em folhas de diferentes espécies vegetais. No entanto, quando considerada a ingestão de 200g/dia, metade do preconizado pela OMS (Organização Mundial de Saúde) para ingestão diária recomendada de legumes, frutas e verduras, infere-se que a quantidade de HPA ingerida por esta via corresponderia a uma dieta de alta exposição MOE (Margin of Exposure) <10 000 próximos aos limites considerados preocupantes pela União Européia. / The PAH are a class of organic contaminants which are formed in burning of sugarcane and fossil fuel. The physicochemical properties are associated with their affinity for fine particulate matter and can therefore be transported over long distances in a short time depending on the weather. The PAH have characteristics of mutagenicity, carcinogenicity and endocrine disruption, because of these characteristics they are substances that have earned interest of researchers in the evaluation of human exposure via differents routes of uptake, and currently the dietary is the less explored. This study aimed to optimize and validate a method for the determination of PAH in vegetables and evaluate the presence of these substances in lettuce , kale and arugula, in locations with and without the influence of sugarcane burning (Araraquara and Itu). The optimized and validated method in this work involves extraction by ultrasound bath and detection by HPLC/FLU, also has acceptable values of LOD and LOQ in accordance with the European Union , 0.3 and 0.9 μg kg- 1 respectively , and the CV (<11.6%) and recovery values (70 ~ 119 %), are also in accordance to the values recommended by ANVISA . Samples of lettuce , arugula and kale grown in two different cities on three sites , Araraquara (rural and urban areas) and Itu (urban area) corresponding to the harvest period (August 2012) and sugarcane off season (March 2013) were analyzed. Concentrations of PAH found in these vegetables were below the levels reported in the literature in leaves of different plant species . However, when considering the intake of 200g/day, half the daily intake of fruits and vegetables recommended by WHO (World Health Organization ) it is inferred that the amount of PAH ingested in this way corresponds to a High exposure diet with MOE ( Margin of exposure) < 10 000 near the limits considered worrisome by the European Union.

First section of chapter 1 deals with gold catalyzed synthesis of ring fused furo[3,2,b]pyrans and furo[3,2,b]furans. Furo[3,2,b]pyrans and furo[3,2,b]furans are ubiquitous structural segments found in a number of natural products including polyether containing marine toxins. Synthesis of furo[3,2,b]pyrans 2a was accomplished from the bis-propargyl ethers 1a, while the synthesis of furo[3,2,b]furans 2b was accomplished from the prenyl propargyl ethers 1b. Scheme 1: Synthesis of furo[3,2,b]pyrans and furo[3,2,b]furans Second section of chapter 1 describes an unusual ring-contraction rearrangement route to functionalized 2,8-oxymethano-bridged di and triquinane. During the course of investigations concerning the total synthesis of 6-oxabicyclo[3.2.1]octane framework containing natural products, an unusual ring-contraction rearrangement sequence was observed in the reaction of 5-substituted 1-methyl-4-isopropenyl-6-oxabicyclo[3.2.1]octan-8-ones 4 to the 2,8-oxymethano-bridged diquinanes 5. The reaction was further demonstrated in the synthesis of triquinane 7 framework. Scheme 2: Synthesis of functionalized di and triquinane In third section of chapter 1 gold catalyzed synthesis of isochromanones and isoquinolones from suitable substituted allyl propargyl ethers was discussed. Synthesis of isochromanones and isoquinolones comprising a quaternary center with high diastereoselectivity was realized via AuCl3 catalyzed tandem intramolecular exo-dig heterocyclization/enol isomerization/Claisen rearrangement sequence in excellent yields. The reaction was general and amenable for the synthesis of structurally diverse analogues. Scheme 3: Synthesis of isochromanones and isoquinolones Forth section of chapter 1 consists of gold catalyzed intramolecular hydroalkoxylation assisted ring opening of furans to the corresponding saturated -keto esters. During the course investigations concerning gold catalyzed intramolecular enyne cyclization reactions, an interesting ring opening of furans in furyl propargyl alcohols to the corresponding tetrahydrofuran appended saturated -keto esters exclusively driven by intramolecular hydroalkoxylation of the alkyne was observed. Reaction of furyl propargyl alcohols without free hydroxyl group, under similar conditions afforded the conjugated enynes involving dehydration/ketalization. Scheme 4: Synthesis of saturated -keto esters and enynes Chapter 2 delineates the enantiospecific synthesis of bicyclo[4.2.2]decadienes 15 via gold catalyzed tandem enyne cyclization, semipinacol rearrangement reaction. Bicyclodecadienes are key structural units of natural products nakafuran-8 and pallescensin B. Scheme 5: Synthesis of bicyclo[4.2.2]decadienes

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Made available in DSpace on 2014-10-09T12:54:47Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:07:30Z (GMT). No. of bitstreams: 0 / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energéticas e Nucleares - IPEN/CNEN-SP

Thesis submitted in fulfilment of the requirements for the degree of Doctor Technologiae: Chemical Engineering, Faculty of Engineering at the Cape Peninsula University of Technology - Cape Town, South Africa / Polycyclic aromatic hydrocarbons (PAHs) are one of the most common and recalcitrant environmental contaminants – known for their potential toxicity, mutagenicity, and carcinogenicity to humans. Biosurfactant application can enhance the biodegradation of PAHs. The main object of this work was to explore the novelty of biosurfactant produced by the isolated strains of Bacillus sp and Pseudomonas aeruginosa grown exclusively on Beta vulgaris, and the modification of the zeolites nanoparticles by the biosurfactant, for enhanced biodegradation of PAHs in soil. Novel biosurfactant-producing strains were isolated from hydrocarbon-contaminated environments, while several agrowaste were screened as primary carbon sources for the expression of biosurfactants, which were quantified using various standardized methods......