Orientador: Sisi Marcondes Paschoal / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T16:04:16Z (GMT). No. of bitstreams: 1 Tangerino_DeboraJulianadosAnjos_M.pdf: 666295 bytes, checksum: d40f37f273e761c768f098ca04d15d89 (MD5) Previous issue date: 2013 / Resumo: A sepse caracteriza-se por uma reação inflamatória sistêmica e um quadro de estresse oxidativo em decorrência da grande formação de espécies reativas de oxigênio (EROs). Há trabalhos que mostram que as plaquetas são importantes neste quadro inflamatório, mas seu verdadeiro papel na sepse ainda não está bem elucidado. Portanto, o objetivo do presente trabalho foi avaliar o efeito temporal do uso do antioxidante N-acetilcisteína (NAC) na resposta inflamatória e na atividade plaquetária em modelo de sepse induzido por lipopolissacarídeo (LPS). Para tanto, ratos controle foram injetados com salina (300 ?l, i.p.) ou NAC (150 mg/kg, i.p.), enquanto os tratados foram injetados com LPS de E. coli (1 mg/kg, i.p.) ou com NAC 30 min ou 6h após a injeção de LPS. Após 48h da injeção de LPS o sangue foi coletado. O número de leucócitos totais e plaquetas foi determinado no sangue periférico. A concentração plasmática de TNF-? foi determinada utilizando kit comercial de ELISA. A agregação plaquetária foi avaliada em agregômetro de dois canais. A determinação de EROs em plaquetas foi feita por citometria de fluxo e a de GMPc por imunoensaio. A determinação da atividade da superóxido dismutase (SOD), glutationa peroxidase (GPx) e glutationa redutase (GR) foi feita através de kits comerciais. O LPS aumentou o número de leucócitos totais e reduziu o de plaquetas no sangue periférico. A NAC, 30 min ou 6h após a injeção de LPS, levou a contagem destas células para números semelhantes ao do grupo injetado com salina ou somente com NAC. A concentração plasmática aumentada de TNF-? nos ratos injetados com LPS foi reduzida por NAC para valores próximos aos encontrados no grupo salina. A agregação plaquetária induzida por ADP (10 ?) não foi afetada por NAC, mas foi 50% menor em ratos tratados com LPS. A inibição da agregação plaquetária foi revertida pela injeção de NAC 30 min ou 6h após a injeção de LPS. O LPS aumentou 2,2 vezes os níveis de GMPc em plaquetas estimuladas com ADP quando comparado com o grupo injetado com salina, o qual foi prevenido por NAC, quer em 30 min ou 6h após a injeção de LPS. Os níveis de GMPc em plaquetas de ratos injetados com NAC foram 45% menores do que os do grupo salina. A produção aumentada de EROs em plaquetas ativadas de ratos injetados com LPS foi reduzida por NAC para níveis semelhantes aos dos controle. A NAC reduziu significativamente a formação de EROs em plaquetas em comparação com o grupo salina. A atividade enzimática da SOD em plaquetas ativadas foi reduzida em 35% por NAC em comparação com o grupo salina. O LPS aumentou, discretamente, a atividade da SOD em plaquetas, sendo este prevenido pelo tratamento com NAC. Diferente do observado com SOD, as atividades enzimáticas da GPx e da GR em plaquetas ativadas foram significativamente aumentadas pelo LPS. A NAC não modificou a atividade da GPx e da GR em comparação com o grupo salina, mas reduziu cerca de 41% e 61% a atividade da GPx e GR, respectivamente, em plaquetas do grupo injetado com LPS. Nossos resultados mostraram que a NAC previne e reverte os efeitos do tratamento de ratos com LPS na atividade plaquetária. O restabelecimento da agregação plaquetária, dos níveis de GMPc e EROs intraplaquetário podem ter sido resultado de uma ação direta de NAC nas plaquetas e/ou em decorrência da melhora do quadro inflamatório do animal / Abstract: Sepsis is an oxidative stress condition characterized by a systemic inflammatory reaction. It has been demonstrated that platelets are important in this inflammatory condition, but their real role in sepsis has not been well elucidated yet. Therefore, the aim of this study was to evaluate the temporal effect of the use of the antioxidant Nacetylcysteine (NAC) in the inflammatory response and platelet activity in a model of sepsis induced by lipopolysaccharide (LPS). Control rats were injected with saline (300 ?l, i.p.) or NAC (150 mg/kg, i.p.), while those treated were injected with LPS from E. coli (1 mg/kg, i.p.) or with NAC 30 min or 6 h after LPS injection. Blood was collected 48 h after LPS injection. Total leukocytes and platelets number was determined in peripheral blood. The plasma concentration of TNF-? was determined using commercial ELISA kit. Platelet aggregation was measured in two-channel aggregometer. Determination of reactive oxygen species (ROS) in platelets was performed by flow cytometry and cGMP by immunoassay. Enzymatic activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) was determinated using commercial kits. LPS increased the total leukocytes number and reduced platelets in peripheral blood. NAC, 30 min or 6 h after LPS injection, brought the cell counts to the similar values of rats injected with saline or with NAC. The increased plasma concentrations of TNF-? in rats injected with LPS was reduced by NAC to values close to those found in the saline group. ADP (10 ?M)-induced platelet aggregation was unaffected by NAC but was 50% lower in rats treated with LPS. Inhibition of platelet aggregation was reversed by the injection of NAC 30 min or 6 h after LPS injection. LPS increased intraplatelet cGMP levels by 2.2-fold compared to the group injected with saline, which was prevented by NAC either 30 min or 6 hours after LPS injection. cGMP levels in activated platelets of rat injected with NAC were 45% lower than those of the saline group. The increased production of ROS in activated platelets from rat injected with LPS was reduced by NAC to levels similar to the control. NAC significantly reduced the formation of ROS in platelets compared to the saline group. SOD activity in stimulated platelets was reduced 35% by NAC compared to the saline group. LPS slightly increased SOD activity in platelets, which is prevented by treatment with NAC. Different from that observed with SOD, the enzyme activities of GPx and GR in activated platelets were significantly increased by LPS. The NAC did not modify the activity of GPx and GR compared with the saline group, but decreased by 41% and 61% the GPx and GR activities, respectively, in platelets of LPS-injected group. Our results showed that NAC prevents and reverses the effects of in vivo LPS on platelet activity. Restoration of platelet aggregation and of intraplatelet cGMP and ROS levels of LPS-injected rats may be caused by a direct action of NAC in platelets or by the improvement of inflammatory condition in the animal / Mestrado / Farmacologia / Mestra em Farmacologia

This thesis focuses on the design and development of novel versatile diamido ligands for transition metal and main group element chemistry. The central concept of this work deal relied on the design of N, N'-disubstituted-1,8-diaminonaphthalene (H2RR’-DAN) as proligands to dianionic diamido ligand scaffolds. These ligands would then be employed for stabilization of main group element (e.g. Li, B, Al) and transition metal (e.g. Ti, Zn) compounds.

The aim of diploma thesis has been development and optimization of method determination of N- nitrososarcosine and N-nitrosoproline in malt by gas chromatography with chemiluminiscence detector. Optimization of extraction method has been performed by response surface method. Quantification has been performed by internal standard method (N-nitrosopipecolic acid, in which matrix effects has been studied. These has been verified in münchen and pilsen malt, therefore matrix-matched calibration has been constructed. The developed method has been aplicated on wheat, münchen and pilsen malt. N- nitrosoproline was detected only in münchen malt and in other cases has been under limit of detection (LOD=4,0 µg/kg). N-nitrososarcosine was in all cases under limit of detection (LOD=3,7 µg/kg). The matrix-matched calibration has been constructed for experimental münchen malt with N-nitrosoproline concentration at 13,2 ± 2,9 µg/kg. Powered by TCPDF (www.tcpdf.org)

In previous studies, we have isolated several marine indole alkaloids and evaluated them in the forced swim test (FST) and locomotor activity test, revealing their potential as antidepressant and sedative drug leads. Amongst the reported metabolites to display such activities was 5-bromo-N,N-dimethyltryptamine. Owing to the importance of the judicious introduction of halogens into drug candidates, we synthesized two series built on a 2-(1H-indol-3-yl)-N,N-dimethylethanamine scaffold with different halogen substitutions. The synthesized compounds were evaluated for their in vitro and in vivo antidepressant and sedative activities using the mouse forced swim and locomotor activity tests. Receptor binding studies of these compounds to serotonin (5-HT) receptors were conducted. Amongst the prepared compounds, 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (1a), 2-(5-bromo-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (1d), 2-(1H-indol-3-yl)-N,N -dimethylethanamine (2a), 2-(5-chloro-1H-indol-3-yl)-N, N-dimethylethanamine (2c), 2-(5-bromo-1H-indol-3-yl)-N,N-dimethylethanamine (2d), and 2-(5-iodo-1H-indol-3-yl)-N,N -dimethylethanamine (2e) have been shown to possess significant antidepressant-like action, while compounds 2c, 2d, and 2e exhibited potent sedative activity. Compounds 2a, 2c, 2d, and 2e showed nanomolar affinities to serotonin receptors 5-HT1A and 5-HT7. The in vitro data indicates that the antidepressant action exerted by these compounds in vivo is mediated, at least in part, via interaction with serotonin receptors. The data presented here shows the valuable role that bromine plays in providing novel chemical space and electrostatic interactions. Bromine is ubiquitous in the marine environment and a common element of marine natural products.

Given a configuration of t indistinguishable pebbles on the n vertices of a graph G, we say that a vertex v can be reached if a pebble can be placed on it in a finite number of "moves". G is said to be pebbleable if all its vertices can be thus reached. Now given the n-path Pn how large (resp. small) must t be so as to be able to pebble the path almost surely (resp. almost never)? It was known that the threshold th(Pn) for pebbling the path satisfies n2clgn≤th(Pn)≤n22lgn, where lg=log2 and c<1/2 is arbitrary. We improve the upper bound for the threshold function to th(Pn)≤n2dlgn, where d>1 is arbitrary.

Les glycoconjugués comme les glycolipides et les glycopeptides sont impliqués dans de nombreux processus biologique, physiologique et pathologique, tels que les interactions cellule-cellule, les infections virales et bactériales, les réponses immunitaires, le cancer, etc. Ces propriétés ont suscité de recherche intensive pour la synthèse de mimes de glycoconjugés pour des applications en biologie et en pharmacie. Cette thèse est consacrée à la synthèse de glycolipides et de glycopeptides liés par la liaison N-oxyamide qui possède une meilleure stabilité métabolique et une facilité de formation de liaison H conduisant à des structures secondaires très intéressantes.Les dérivés de pyranoid glycoaminooxy acides fonctionnés en positions 2 et 6 du sucre sont synthétisés à partir du methyl alpha-D-glucopyranoside, puis transformés en N-oxyamide glycolipides. En tant que nouveaux mimes de glycoglycérolipides et glycosphingolipides, les N-oxyamide beta-glycolipides possédant une ou deux chaines lipidiques sont préparés à partir du glucose ou du galactose penta-acétate et de (S)-1,2-di-O-benzyl-glycérol.De plus, une synthèse stéréosélective de (2R) et de (2S)-3-beta-O-glycosyl aminooxy esters a été réalisée à partir du (2R)-beta-glycoglycérol, avec la réaction de Mitsunobu et l’épimérisation de Lattrell-Dax comme étapes clés. Les N-oxyamide glycopeptides ont pu être préparés à partir de glycosyl aminooxy esters orthogonalement protégés. / As part of glycoconjugate family, glycolipids and glycopeptides are involved in a variety of important biological, physiological and pathological processes, such as cell-cell interactions, viral and bacterial infections, immune response, cancer progression, etc. Synthesis of glycoconjugate mimics has attracted intensive research interest for biological and pharmaceutical applications. This thesis was devoted to the synthesis of N-oxyamide-linked glycolipids and glycopeptides, since N-oxyamide-containing compounds have shown improved metabolic stability, and interesting secondary structures due to the easy H-bond formation property of N-oxyamide compounds.From methyl alpha-D-glucopyranoside, the 2,6-functionalized pyranoid glycoaminooxy acid derivatives have been successfully prepared as a multifunctional building block for further derivatization to new N-oxyamide glycolipids. From glucose or galactose pentaacetate and (S)-1,2-di-O-benzyl-glycerol, we have successfully achieved the first synthesis of N-oxyamide-linked beta-glycolipids with one or two lipids chains, as novel mimics of glycoglycerolipids and glycosphingolipids.In addition, the (2R) and (2S)-3-beta-O-glycosyl aminooxy esters have been stereoselectively synthesized from (2R)-beta-glycoglycerol, with Mitsunobu reaction and Lattrell-Dax epimerization as key steps. N-Oxyamide-linked glycopeptides have been prepared from the orthogonally protected glycosyl aminooxy esters.

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The main objective of this project is the study of heterogeneous metallic catalysts for the production of fine chemicals and elimination of ultra low concentration of ethylene with horticultural applications. Development of new active and selective catalysts in industrial processes has been possible due to a simultaneous application of rational design catalysts and characterization techniques of materials. With this purpose, heterogeneous metallic catalysts with properties to reduce selectively nitro groups when other sensitive functions are present have been developed. Monometallic and bimetallic Pt and Au catalysts were estudied in reductive coupling reactions with nitrocompunds, aldehydes and H2 which have allowed to evaluate variables as support effect, solvent, metal promoter and intensity of heat treatment on their catalytic behavior.The proposed procedure offers an efficient and sustainable alternative for the production of nitronas, imines or secondary amines through a metal heterogeneous catalysts that does not require the use of soluble, often toxic, additives. On the other hand, it has been shown that silver supported on zeolite is able to adsorb high amounts of ethylene in ultra low concentrations in air (10 ppm). Taking this into account, the influence of concentration of active species according with framework used was investigated. The influence of molecules, such as H2O or CO2, in competition for the active sites on the adsorption of ethylene was studied in order to optimize their behavior in processes of adsorption of trace amounts of ethylene with horticultural applications. / La presente tesis doctoral tiene como principal objetivo el estudio de catalizadores metálicos heterogéneos para la obtención de productos de química fina y la eliminación de trazas de etileno por adsorción con aplicaciones hortícolas. Gracias a la aplicación simultánea de técnicas de diseño racional de los catalizadores y a técnicas de caracterización fundamental de los materiales, ha sido posible el desarrollo de nuevos catalizadores activos y selectivos en procesos de interés industrial. Con este fin, se han desarrollado catalizadores metálicos heterogéneos con propiedades exclusivas para hidrogenar quimioselectivamente grupos nitro en presencia de otros grupos funcionales reducibles. El estudio de catalizadores monometálicos y bimetálicos de Pt, Au soportados para reacciones de acoplamiento reductivo de nitrocompuestos, aldehídos e H2 ha permitido evaluar la influencia de las principales variables de síntesis de los materiales sobre su comportamiento catalítico, incluyendo el efecto del tipo de soporte utilizado, el disolvente empleado, la introducción de diferentes promotores metálicos y la intensidad del tratamiento térmico realizado. El procedimiento propuesto ofrece una alternativa eficiente y sostenible para la producción industrial de nitronas, iminas y/o aminas secundarias mediante el uso de catalizadores metálicos heterogéneos que no requieren el uso de aditivos tóxicos. Por otra parte, se ha mostrado que plata soportada sobre zeolitas es capaz de adsorber elevadas cantidades de etileno en concentraciones de 10 ppm en aire. Así, se ha estudiado la influencia de la estructura zeolítica empleada en la concentración de especies activas para la adsorción de etileno, en adsorbentes Ag-zeolita. Con el fin de optimizar su comportamiento en procesos de adsorción de trazas de etileno con aplicaciones horticulturales se ha estudiado la influencia de moléculas, como H2O y/o CO2, en la competencia por los sitios activos en la adsorción de etileno. / Aquesta tesi doctoral té com a principal objectiu l'estudi de catalitzadors metàl¿lics heterogenis per a l'obtenció de productes de química fina i l'eliminació de traces d'etilÿ per adsorció amb aplicacions hortícoles. Gràcies a l'aplicació simultània de tÿcniques de disseny racional dels catalitzadors i a tÿcniques de caracterització fonamental dels materials, ha sigut possible el desenvolupament de nous catalitzadors actius i selectius en processos d'interÿs industrial. S'hi han desenvolupat catalitzadors metàl¿lics heterogenis amb propietats exclusives per a hidrogenar quimioselectivament grups nitro- en presÿncia d'altres grups funcionals reduïbles. L'estudi de catalitzadors monometàl¿lics i bimetàl¿lics de Pt, Au, suportats per a reaccions d'acoblament reductiu de nitrocompostos, aldehids i H2, ha permÿs avaluar la influÿncia de les principals variables de síntesi dels materials sobre el seu comportament catalític, inclòs l'efecte del tipus de suport utilitzat, el dissolvent emprat, la introducció de diferents promotors metàl¿lics i la intensitat del tractament tÿrmic. El procediment proposat ofereix una alternativa eficient i sostenible per a la producció industrial de nitrones, imines i/o amines secundàries mitjançant l'ús de catalitzadors metàl¿lics heterogenis amb propietats exclusives per a hidrogenar quimioselectivament grups nitro- en presÿncia d'altres grups funcionals reduïbles. D'altra banda, s'hi ha mostrat que la plata sobre zeolites és capaç d'adsorbir elevades quantitats d'etilÿ en concentracions de 10 ppm en aire. Així, s'ha estudiat la influÿncia de l'estructura zeolítica emprada en la concentració d'espÿcies actives per a l'adsorció d'etilÿ, en adsorbents Ag-zeolita. Amb l'objectiu d'optimitzar-ne el comportament en processos d'adsorció de traces d'etilÿ amb aplicacions horticulturals, s'ha estudiat la influÿncia de molÿcules, com ara H2O i/o CO2, en la competÿncia pels llocs actius en l'adsorció d'etilÿ. / Cisneros Reyes, LY. (2017). Metales Soportados para Síntesis de Nitronas y Adsorción de Etileno en corrientes de Aire [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/90434

Nitrogen recovery and contribution to production agricultural systems are critical services provided by cover crops investigated in this study. Research was conducted to evaluate the effect of simulated residual N (SRN) on N recovery in various winter cover crop systems (CCS) and subsequent effects on corn N uptake. Biomass, C and N measurements, 15N recovery, and sources of N acquisition were quantified among CCS. Subsequently, CCS and SRN effects on corn productivity and N status were quantified. Grass-included CCS had the greatest N scavenging ability by CCS termination, though they had negative or neutral effects on corn N acquisition. Brassicas-included CCS were prolific early season N scavengers, though winterkill may have negated this effect. Legumes-included CCS generally accumulated large quantities of N and had narrow C:N ratios, positively affecting corn N acquisition. This study highlights the importance of context-specific CCS selection for N conservation.