Orientador: Pedro Luiz Rosalen / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-19T15:53:46Z (GMT). No. of bitstreams: 1 DelFiol_FernandodeSa_M.pdf: 1505001 bytes, checksum: 265a879fb9127a4758242b8ad95fd302 (MD5) Previous issue date: 1994 / Resumo: A proposta do presente estudo foi avaliar a interferência da alimentação na absorção gastrointestinal de flúor ingerido através de dentifrício fluoretado. Dezoito voluntários adultos jovens foram submetidos a três situações de conteúdo estomacal, jejum, café da manhã e almoço e à ingestão de um dentifrício em 3 concentrações; placebo, 550 e 1100 ppmF, ou seja, em ocasiões diferentes ingeriram um dentifrício em cada situação de conteúdo gástrico. Foram feitas coletas de urina 24 horas anteriores e posteriores ao experimento e a partir da ingestão do dentifrício, amostras de saliva foram coletadas nos tempos (hora) 0; 0,25; 0,5; 0,75; 1,0; 2,0; 3,0; 8,0 e 24. Através da área de concentração salivar e da quantidade de flúor excretada em cada tratamento e pôde-se notar uma queda na absorção em torno de 19% quando da ingestão de flúor após o café da manhã e de aproximadamente 33% quando da ingestão de flúor após uma refeição tipo almoço / Abstract: The aim of the present study was to determine the influence of feed in the gastrointestinal absorption of fluoride ingested as fluoride dentifrices. Eighteen young volunteers were submited to three situations of stomachal contents; fasting stomach, breakfast and lunch and then to ingest some fluoride dentifrice in three different concentrations; placebo, 550 and 1100 ppmF, i.e., in different occasions they ingested one dentifrice in a situation of stomachal content. Urine was colected 24h before and after the experiment and as soon they ingested the dentifrice, saliva samples were colected in time (hour) 0; 0,25; 0,5; 0,75; 1,0; 2,0; 3,0, 8,0 and 24,0. Data from salivary fluoride concentration (ASC) and F urinary output was determined. In the present study it was found that breakfast and lunch consumed prior to ingestion of fluoride reduces fluoride absorption by 19% and 33% respectiviJy, compared to ingestion on a fasting stomach / Mestrado / Farmacologia / Mestre em Odontologia

Les composés fluorés ont montré une importance croissante dans le développement d'agents pharmaceutiques en raison des propriétés exceptionnelles de l'atome de fluor. Dans cette thèse, nous nous sommes concentrés sur la synthèse des composés énantiopurs contenant de l'azote.A partir de l'aldimine trifluorométhylée, une réaction d’aza-Baylis-Hillman asymétrique a été réalisée et a permis d’obtenir un nouvel acide (R)-α-méthylène-β-CF3-β-aminé avec un bon rendement et une excellente diastéréosélectivité. Puis, en utilisant une réaction d’allylation dans les conditions de Barbier, de nouveaux acides aminés trifluorométhylés cycliques à cinq ou six chaînons ont été obtenus avec de bons rendements et d’excellents diastéréosélectivités. En particulier des acides γ et β-aminés, comme la CF3-β-proline, qui est très intéressante dans la synthèse peptidique.Enfin, grâce à l'addition d'éther de vinyle sur l’aldimine trifluorométhylée, différentes amines trifluorométhylées ont été obtenues. Parmi ces composés, les amino-alcools CF3 qui sont très utiles pour la conception de médicaments et dans la synthèse asymétrique, et les amines cycliques trifluorométhylées qui peuvent servir de bon substrat pour synthétiser des composés CF3-cycliques plus fonctionnalisés. / Fluorinated compounds have shown a growing importance in the development of pharmaceutical agents owing to the outstanding properties of the fluorine atom. In this thesis, we focused on the synthesis of enantiopure trifluoromethyl nitrogen-containing compounds.Starting from the trifluoromethyl aldimine, firstly, an asymmetric aza-Baylis–Hillman reaction was realized with high reaction rates, and diastereoselectivities, and the previously unknown enantiomerically pure (R)-α-methylene β-CF3 β-amino acid was obtained in good yield. Then, through aza-Barbier reaction, the five-membered and six-membered trifluoromethyl cyclic amino acids were obtained, including β-amino acid and γ-amino acid, especially CF3-β-proline, which is very interesting in the further peptide synthesis.Finally, through the addition of vinyl ether to imine, different novel trifluoromethylated amines were afforded. Among these compounds, CF3-amino alcohols are very useful in drug design and asymmetric synthesis, and enantiopure CF3-cyclic amine is a very good substrate to synthesize more functionalized CF3-cyclic compounds.

L’atome de fluor est un élément essentiel de notre quotidien. Il est indispensable pour le développement des batteries, de la réfrigération (Fréon), des cristaux liquides qui constituent nos écrans de téléphone ou encore des matériaux (Téflon®). Mais c’est surtout dans les sciences du vivant que le fluor joue un rôle primordial. L’introduction d’un atome de fluor modifie les propriétés physico-chimiques d’une molécule, permettant ainsi de moduler et d’améliorer profondément son activité biologique. Son introduction dans les molécules organiques représente donc un défi majeur pour les chimistes, qui nécessite sans cesse le développement de nouveaux réactifs de fluoration et perfluoroalkylation.Parmi ceux-ci, les sulfoximines perfluorées sont des réactifs de perfluoroalkylation électrophile, nucléophile ou radicalaire. De plus, les sulfoximines perfluorées possèdent des propriétés singulières ayant des applications en sciences des matériaux et du vivant.Mes travaux de thèse s’inscrivent dans la volonté de notre laboratoire de mettre au point une nouvelle voie d’accès générale aux sulfoximines fluorées ainsi qu’à la synthèse de sulfoximines hautement fonctionnalisées. Ma thèse a également pour but l’étude des sulfilimino iminiums, dont la synthèse dérive de celle des sulfoximines et qui sont des réactifs très efficaces et polyvalents pour des réactions perfluoroalkylation par catalyse photoredox. / Fluorine atom is essential in our everyday life. It is necessary for the development of battery, refrigeration (Fréon), liquid crystals which constitute the screens of phones, or materials (Téflon®). But its main role is in life sciences. The introduction of a fluorine atom modifies the physical and chemical properties of organic molecules, allowing to modulate and to enhance their biological activities. Its introduction in organic molecules constitutes a key challenge for chemists, which necessitates continually the development of new reagents for fluoration or perfluoroalkylation reactions. Among these, perfluorinated sulfoximines are electrophilic, nucleophilic or radical perfluoroalkylating reagents. Moreover, perfluorinated sulfoximines have peculiar properties with uses in material or life sciences.My PhD work falls within the project of our laboratory to develop a new general acces to perfluorinated sulfoximines and the synthesis of highly functionalized sulfoximines. My PhD work also deals with the synthesis of sulfilimino iminiums, derived from sulfoximines, which are efficient and versatile reagents for visible light-induced perfluoroalkylation reactions.

Alkaline glutaraldehyde (GTA) has been used as a high level chemical disinfectant and sterilant for many years and is known to kill a broad spectrum of organisms ranging from vegetative eukaryotes to bacterial endospores. Although the mechanism of sporicidal action has been studied on numerous occasions, GTA's exact mechanism(s) of action are still debated. In addition to the uncertainty of GTA's mechanism(s) of action, GTA has also shown significant variability in the time required to kill endospores and naked viruses. A better knowledge of the lethal mechanism(s) of GTA is needed to understand this discrepancy in kill times for GTA against spores of different species. Similar trends have been observed in GTA's activity against non-enveloped viruses. Based on previous work, one proposed major mechanism of GTA's sporicidal activity is related to the number of available primary amines located on the surface of microbes. In this study, we have compared the efficacy of GTA on spores from 5 Bacillus species. We have also developed a method for staining these spores with amine reactive dyes to create fluorescent profiles correlating to the abundance of free amino groups on each spore type. We also describe a method for staining non-enveloped viruses to identify exposed primary amino groups on capsid proteins that may act as targets for GTA, using amine reactive Gold nanoparticles. We found that GTA 6-Log10 reduction times for various spore types varied at both the batch and species level. Spore coat thickness and fluorescence were useful tools in predicting the susceptibility of spores to GTA. Amine reactive gold particles (AuNPs) also proved useful in identifying virus susceptibility to GTA. Ultimately, more reliable disinfection testing methods are needed, and caution should be used when trying to extrapolate data generated from surrogate organisms to other species.

Athanasios Markos Abstract This Thesis deals with denitrogenative transformations of N-fluoroalkyl-1,2,3-triazoles, easily available heterocycles via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of safe and stable N-fluoroalkyl azides and alkynes. The introductory chapter describes general approaches towards N1-substituted 1,2,3- triazoles, methods of N1-,-difluoroalkyl-1,2,3-triazoles preparation and both, transition metal-catalyzed and transition metal-free transformations of N1-substituted 1,2,3- triazoles. In the first part of the Thesis, rhodium-catalyzed reactions of N-fluoroalkyl-1,2,3-triazoles are described. Rhodium-catalyzed reactions of N-fluoroalkyl-1,2,3-triazoles in presence of suitable reagents provide access to five-membered N-fluoroalkyl heterocycles, 2- fluoroalkyl oxazoles and ketamides. In the second part of the Thesis, both Brønsted and Lewis acid-mediated transformations of N-fluoroalkyl-1,2,3-triazoles leading to stereodefined N-alkenyl compounds, such as enamides, enimines, amidines and other are discussed. The robustness of the method is showcased on gram scale syntheses and preparation of a drug analogue. At last, thermally-induced rearrangement of N-fluoroalkyl-1,2,3-triazoles to 3-fluoroalkyl-2H- azirines and the proposed mechanism of the reaction are described.

Les O-glycoconjugués et les dérivés glycosidiques sont des composés naturels impliqués dans de nombreux processus biologiques. Cependant, leurs propriétés sont grevées par la médiocre stabilité in vivo de la liaison osidique. Il est donc intéressant de développer des mimes non hydrolysables. Nous nous sommes intéressés au remplacement de l’oxygène intracyclique par un groupement gem-difluorométhylène.La synthèse d’analogues difluorocarbocycliques de 5-désoxypentofuranoses et de 1-amino-5-désoxypentofuranoses a été décrite. La synthèse comporte une addition dePhSeCF2TMS sur des aldéhydes dérivés de sucres ou sur les tert-butanesulfinylimines correspondantes, suivie d’une cyclisation radicalaire. La diastéréosélectivité de ces deux étapes-clés a été étudiée, puis cette stratégie de synthèse a été appliquée à la synthèse deCF2-carbasucres, notamment l’analogue CF2-carbocyclique du D-arabinose. / O-Glycoconjugates and carbohydrate-based molecules are natural compoundsimplied in many biological processes. However, their properties are burdened by the low invivo stability of the osidic bond. It is thus interesting to develop non hydrolyzable mimetics.We were interested in the replacement of the intracyclic oxygen by a gem-difluoromethylenegroup.The synthesis of difluorinated carbocyclic analogues of 5-deoxypentofuranoses and1-amino-5-deoxypentofuranoses is described. The sequence involves an addition ofPhSeCF2TMS to carbohydrate-derived aldehydes or their corresponding tertbutanesulfinyliminesfollowed by a radical cyclization. The stereochemical outcome of these two key steps was studied, and then this strategy was applied to CF2-carbasugars, inparticular of the CF2-carbocyclic analogue of D-arabinose.

The incorporation of the trifluoromethyl and perfluoroalkyl motifs into organic compounds has been a hot topic in synthetic organofluorine chemistry. There is a plethora of methods for the introduction of the CF3 moiety at carbon, oxygen and sulfur centers. In sharp contrast, methods for synthesizing N-trifluoromethyl and N-perfluoroalkyl compounds are very limited and new approaches are highly sought-after. The scarcity of these compounds prompted us to develop reagents capable of transferring the perfluoroalkyl unit to nitrogen atom. To fulfil this purpose, we have regarded azidoperfluoroalkanes as ideal reagents, therefore, this thesis is concerned with the synthesis and applications of these azides. The first part describes the preparation of azidoperfluoroalkanes. Upon activation by cesium fluoride, TMSCF3 transfers the trifluoromethyl group to an electrophilic azide to produce the desired azidotrifluoromethane. Longer carbon chain azidoperfluoroalkanes were prepared in a similar way, starting from the corresponding organosilane. A different synthetic strategy was applied for the preparation of azidopentafluoroethane where the perfluoroalkyl anion was generated from pentafluoroethane with n BuLi, followed by the addition of tosyl azide. The isolation of these fluorinated azides was...

Syftet med denna litteraturstudie är att beskriva vilken kariesförebyggande effekt olika fluorbehandlingar har bland personer med muntorrhet. Vetenskapliga artiklar söktes i databaserna PubMed och Cinahl. Åtta artiklar relevanta för denna litteraturstudie valdes ut för granskning. Artiklarna kvalitetsbedömdes med hjälp av en granskningsmall för kvantitativa studier. Resultaten visade att god munhygien i kombination med 1 % NaF-gel i skenor har visat sig vara en adekvat behandlingsmetod mot karies hos patienter med muntorrhet. En studie som jämfört olika koncentrationer av NaF-gel i skenor har inte uppvisat någon skillnad avseende kariesincidensen i de båda grupperna.  Jämförelser mellan NaF-gel i skenor med munskölj och dessa i kombination visade en minskning av antal extraktioner men antalet lagningar ökade oavsett behandling. Kariesincidensen visade ingen skillnad mellan NaF-gel i skenor jämfört med tandborstning med 1350 ppm fluor.  Att använda SnF2-gel som vid tandborstning var effektivas mot rotkaries i jämförelse med NaF-gel i kombination med munskölj. Kariesincidensen visade sig vara likvärdig i jämförelse mellan IFRS och fluorgel. Genom att använda 1 % NaF-gel 5 min varannan dag reduceras demineraliseringsprocessen effektivast.

Multiple sclerosis is a complex disease and one for which the aetiology remains largely unanswered. Anti-dsDNA antibodies have been found intrathecally and bordering lesions in multiple sclerosis patients and in view of their known pathogenity in lupus nephritis the aim of this project was to further investigate their role in multiple sclerosis. Using the acute experimental allergic encephalomyelitis (EAE) model in the Lewis rat, the inflammatory phase of disease was profiled using immunohistological and ELISA methods and was related to clinical sign severity. The parameters of interest were central nervous system deposits of IgM, IgG, B cells and C3 and anti-DNA antibodies in sera, cerebrospinal fluid and in situ. In situ evaluation of anti-dsDNA antibodies was also performed in tissue taken from Biozzi (AH) mice (relapsing/remitting EAE model) and from a multiple sclerosis patient. Inflammatory deposits specifically at sites of perivascular cuffing were found to increase with increasing clinical sign severity. At the time clinical signs had plateaued in the Lewis rat, intrathecal anti-dsDNA antibodies were at their highest level and anti-ssDNA antibodies at their lowest. The latter possibly due to their involvement in the `clearing-up¿ process following tissue damage. Using novel DNA probes fluorescence suggestive of the presence of anti-dsDNA iii antibodies was seen in both animal and human tissue. Within human tissue the antibodies appeared to accumulate around active lesions and within vessels, raising the question of these antibodies having differing location dependent functions. EAE models have the potential to investigate these findings further and to evaluate new therapies. / Covance Laboratories Ltd.

La cavité buccale offre un espace en perpétuelles interactions. Différentes structures y sont présentes dont les muqueuses, l'émail, la salive, les matériaux de restaurations et la microflore. Ces microorganismes peuvent s'organiser en biofilms, échapper à la défense immunitaire et provoquer plusieurs pathologies, dont les candidoses. L'objectif de cette étude est d'analyser les interactions entre Candida albicans et plusieurs matériaux de restauration dentaire. Nos résultats ont montré que C. albicans adhère et prolifère moins bien sur le verre ionomère comparativement aux autres biomatériaux utilisés. L'adhésion est suivie d'une formation de biofilms dépendant du type de matériau. Nous avons aussi démontré que le fluor réduit de façon significative l'adhésion, la croissance et la transformation de C. albicans. C'est la première étude qui rapporte l'effet du fluor sur la virulence de Candida. Ceci suggère le choix de matériau dentaire pour des restaurations pérennes et la possibilité d'utiliser du fluor pour réduire les candidoses.