Molecular imaging involves the development of probes which can specifically label a certain object in the body at cellular or subcellular level. This thesis consists of three parts, each involving the development of novel labelling methods for viruses or virus-like particles with specific applications. Virus-like particles (VLP) derived from the E. coli bacteriophage Qβ are widely employed as a nano-carrier for drugs and vaccines, but a powerful method for tracing its circulation without affecting its structure is yet to be developed. In the first part of the thesis, the electrophilic fluorine source ¹⁹F-Selectfluor^TM was employed for introducing single fluorine atoms on Qβ VLPs. For the 'tag-and-modify' approach, site-selective electrophilic C-F bond formation was achieved on the dehydroalanine (Dha) amino acid tag of VLPs under aqueous conditions. Chemoselective electrophilic aromatic fluorination on tyrosine residues were also achieved using the same reagent by manipulating the amino acid sequence. Similar results were observed in conditions required for ¹⁸F-Selectfluor™ reaction, indicating the potential of this technique for positron emission tomography (PET) imaging. In addition, there is a lack of in situ technique for tracking the functional status of Qβ VLPs and hence the release of cargos. In the second part of the thesis, a simple way to monitor the disassembly of ¹⁹F-labelled Qβ VLPs by ¹⁹F NMR spectrosocpy is reported. Analysis of resonances, using experiments under a range of conditions, allowed determination not only of the intact particle but also the disassembled multimeric species and even smaller peptides upon digestion by cells. This in turn allowed mutational redesign of disassembly and testing in both bacterial and mammalian systems as a strategy for the creation of putative, targeted-VLP delivery systems. In the third part of the thesis, a new type of rhodamine B fluorescent dye functionalised with a 2-imino-2-methoxyethyl (IME) group is reported. The amidine linkage formed between the IME group and lysine residue retains the pKaH of the original side chain, which cannot be achieved using commercially available conjugating dyes. This in turn minimises the change in net charge hence virus infectivity following virus labelling. By employing adenovirus (AV) as an example, the IME dye was shown to be a better choice in retaining virus infectivity compared to dyes linked with other coupling groups. In addition, preliminary experiments on dengue virus with the synthesised dyes were also performed.

Orientador: Juliano Pelim Pessan / Banca: Marília Afonso Rabelo Buzalaf / Banca: Alberto Carlos Botazzo Delbem / Resumo: O uso de fluoretos tem contribuído para o declínio da prevalência da cárie observado nas últimas décadas, porém um aumento na prevalência da fluorose dentária tem sido observado concomitantemente. Alternativas como a redução do pH e da concentração de fluoreto (F) dos dentifrícios têm sido estudadas na tentativa de melhorar a efetividade clínica dos mesmos, sem afetar sua eficácia anti-cárie. Considerando a escassez de estudos com metodologias in vivo avaliando a retenção intrabucal de F após a utilização de formulações aciduladas, o presente estudo avaliou a influência do pH e da concentração de fluoreto (F) de dentifrícios na retenção de F pela saliva, biofilme e fluido do biofilme. Voluntários (n=22) utilizaram dentifrícios contendo 0 (Placebo), 550 (DCRF - dentifrício com concentração reduzida de F) e 1100 ppm F (DC - dentifrício convencional), em pH 4,5 e 7,0, e escovaram seus dentes 3 vezes/dia seguindo um protocolo duplo-cego e cruzado. Amostras de saliva e biofilme dentário foram coletadas após 7 dias de uso dos dentifrícios, 1 e aproximadamente 12 horas após a última escovação. As análises de F e cálcio (Ca) foram realizadas com o eletrodo invertido após tamponamento com TISAB III e pelo método Arsenazo III, respectivamente. Os dados foram analisados por ANOVA fatorial, teste de Tukey HSD e coeficiente de correlação de Pearson (p<0,05). As concentrações de F no fluido do biofilme 1h após a escovação com o DCRF acidulado não diferiram das observadas para o DC neutro, sendo ambas significativamente mais altas que as obtidas com o placebo; este padrão, entretanto, não foi observado para o biofilme e saliva. Observou-se a ausência de um padrão definido para as concentrações de Ca nestes compartimentos, porém correlações significativas foram observadas entre as concentrações de F e Ca na saliva e no biofilme. De acordo com protocolo do estudo, concluiu-se ... / Abstract: The use of fluorides has contributed to the decline in caries prevalence observed in the last decades, however an increase in the prevalence of dental fluorosis has been observed concomitantly. Alternatives such as the reduction of the pH and fluoride (F) concentration of dentifrices have been studied as an attempt to improve their clinical effectiveness without affecting its anti-caries efficacy. Given the scarcity of in vivo studies assessing intraoral fluoride retention after using acidic formulations, the present study evaluated the influence of pH and F concentration of dentifrices on F uptake by saliva, biofilm and biofilm fluid. Volunteers (n = 22) used dentifrices containing 0 (Placebo), 550 (LFD - low-fluoride dentifrice) and 1100 ppm F (CD - conventional dentifrice) at pH 4.5 and 7.0, and brushed their teeth 3 times/day following a double-blind, crossover protocol. Saliva and dental biofilm samples were collected after 7 days of using the dentifrices, 1 and approximately 12 hours after last brushing. F and calcium (Ca) analysis were performed with the inverted electrode after buffering with TISAB III and the Arsenazo III method, respectively. Data were analyzed by factorial ANOVA, Tukey's HSD test and Pearson's correlation coefficient (p <0.05). F concentrations in the biofilm fluid 1h after brushing with acidic LFD were similar to those observed for neutral CD, both being significantly higher than values found for the Placebo; this pattern, however, was not observed for the biofilm and saliva. No defined trend was observed for Ca concentrations in these compartments, but significant correlations were observed between Ca and F concentrations in saliva and in the biofilm. According to the study protocol, it was concluded that pH influenced the uptake of F by the biofilm fluid, having little or no influence on the uptake by the biofilm and saliva, respectively. / Mestre

Made available in DSpace on 2014-10-09T12:49:05Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:10:00Z (GMT). No. of bitstreams: 1 09676.pdf: 487919 bytes, checksum: 0745fbc8dd8d4e9f050ed47878924b0a (MD5) / Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia) / IPEN/D-MPLO / Instituto de Pesquisas Energeticas e Nucleares, IPEN/CNEN-SP; Faculdade de Odontologia, Universidade de Sao Paulo

Made available in DSpace on 2014-06-11T19:29:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-03-12Bitstream added on 2014-06-13T19:59:13Z : No. of bitstreams: 1 000738492.pdf: 3114256 bytes, checksum: 838875375dce954365c271d4098e4b23 (MD5) / O uso de fluoretos tem contribuído para o declínio da prevalência da cárie observado nas últimas décadas, porém um aumento na prevalência da fluorose dentária tem sido observado concomitantemente. Alternativas como a redução do pH e da concentração de fluoreto (F) dos dentifrícios têm sido estudadas na tentativa de melhorar a efetividade clínica dos mesmos, sem afetar sua eficácia anti-cárie. Considerando a escassez de estudos com metodologias in vivo avaliando a retenção intrabucal de F após a utilização de formulações aciduladas, o presente estudo avaliou a influência do pH e da concentração de fluoreto (F) de dentifrícios na retenção de F pela saliva, biofilme e fluido do biofilme. Voluntários (n=22) utilizaram dentifrícios contendo 0 (Placebo), 550 (DCRF – dentifrício com concentração reduzida de F) e 1100 ppm F (DC – dentifrício convencional), em pH 4,5 e 7,0, e escovaram seus dentes 3 vezes/dia seguindo um protocolo duplo-cego e cruzado. Amostras de saliva e biofilme dentário foram coletadas após 7 dias de uso dos dentifrícios, 1 e aproximadamente 12 horas após a última escovação. As análises de F e cálcio (Ca) foram realizadas com o eletrodo invertido após tamponamento com TISAB III e pelo método Arsenazo III, respectivamente. Os dados foram analisados por ANOVA fatorial, teste de Tukey HSD e coeficiente de correlação de Pearson (p<0,05). As concentrações de F no fluido do biofilme 1h após a escovação com o DCRF acidulado não diferiram das observadas para o DC neutro, sendo ambas significativamente mais altas que as obtidas com o placebo; este padrão, entretanto, não foi observado para o biofilme e saliva. Observou-se a ausência de um padrão definido para as concentrações de Ca nestes compartimentos, porém correlações significativas foram observadas entre as concentrações de F e Ca na saliva e no biofilme. De acordo com protocolo do estudo, concluiu-se... / The use of fluorides has contributed to the decline in caries prevalence observed in the last decades, however an increase in the prevalence of dental fluorosis has been observed concomitantly. Alternatives such as the reduction of the pH and fluoride (F) concentration of dentifrices have been studied as an attempt to improve their clinical effectiveness without affecting its anti-caries efficacy. Given the scarcity of in vivo studies assessing intraoral fluoride retention after using acidic formulations, the present study evaluated the influence of pH and F concentration of dentifrices on F uptake by saliva, biofilm and biofilm fluid. Volunteers (n = 22) used dentifrices containing 0 (Placebo), 550 (LFD – low-fluoride dentifrice) and 1100 ppm F (CD – conventional dentifrice) at pH 4.5 and 7.0, and brushed their teeth 3 times/day following a double-blind, crossover protocol. Saliva and dental biofilm samples were collected after 7 days of using the dentifrices, 1 and approximately 12 hours after last brushing. F and calcium (Ca) analysis were performed with the inverted electrode after buffering with TISAB III and the Arsenazo III method, respectively. Data were analyzed by factorial ANOVA, Tukey´s HSD test and Pearson´s correlation coefficient (p <0.05). F concentrations in the biofilm fluid 1h after brushing with acidic LFD were similar to those observed for neutral CD, both being significantly higher than values found for the Placebo; this pattern, however, was not observed for the biofilm and saliva. No defined trend was observed for Ca concentrations in these compartments, but significant correlations were observed between Ca and F concentrations in saliva and in the biofilm. According to the study protocol, it was concluded that pH influenced the uptake of F by the biofilm fluid, having little or no influence on the uptake by the biofilm and saliva, respectively.

Resumo: Foi objetivo validar o modelo de ciclagem de pH verificando relação dose-resposta de materiais que liberam flúor, pela sua capacidade em reduzir a desmineralização e promover a remineralização in vitro. Selecionou-se 120 blocos de esmalte (4x3 mm), pelo teste de microdureza de superfície (SMH), sendo avaliadas 4 distâncias (150, 300, 450 e 600 μm) do material. Lesão de cárie artificial foi induzida (n=48) para o teste de microdureza de superfície pós-cárie (SMH1). Corpos-de-prova foram confeccionados (n=96) e adaptados aos blocos dos grupos: Z 100, Fluroshield, Vitremer e Vitremer diluído ¼, sendo o restante (n=24) do grupo controle. Os espécimes foram submetidos à ciclagem de pH, para inibir a desmineralização e promover a remineralização. Realizou-se teste de microdureza de superfície final (SMH2) para cálculo da porcentagem de alteração (%SMHA) e recuperação (%SMHR). Tanto a porcentagem de alteração (ΔZA) como a de recuperação (ΔZR) do conteúdo mineral foi calculada. Fez-se a leitura de flúor das soluções (mg F) e do esmalte (mg F/mm3). Correlação negativa foi observada entre %SMHA e mg F/mm3 (r=-0,9983; p=0,0000001), %SMHA e mg F (r=-0,9884; p=0,0000001), também entre DZA e mg F/mm3 (r=-0,9762; p=0,0048) e DZA e mg F (r=-0,9975; p=0,0000001); e positiva entre mg F/mm3 e mg F (r=0,9802; p=0,0018). Houve correlação positiva entre %SMHR e mg F/mm3 (r=0,9770; p=0,004), %SMHR e mg F (r=0,9939; p=0,0000001), e também entre mg F e mg F/mm3 (r=0,9819; p=0,0010). Em relação ao DZR, houve correlação com mg F/mm3 (r=0,9853; p=0,0002) e mg F (r=0,9975; p=0,0000001). O modelo de ciclagem de pH foi validado pela verificação in vitro da relação dose-resposta de materiais que liberam flúor na desmineralização e na remineralização do esmalte. / Abstract: The aim was valid pH-cycling model verifying dose-response relationship of the fluoride-releasing materials by its capacity in reduce the demineralization and promote the remineralization in vitro. Bovine enamel blocks (n=120) were selectioned by surface microhardness test (SMH) in 4 distances evaluated (150, 300, 450 and 600 mm) of material. Artificial caries lesions were induced (n=48) for post caries surface microhardness test (SMH1). Samples of the materials Z 100, Fluroshield, Vitremer and Vitremer ¼ diluted were prepared (n=96) and adapted to enamel blocks. For the control group, no material was used (n=24). The specimens were submitted to pHcycling to inhibit demineralization and other to promote remineralization. Final surface microhardness test was assessed (SMH2) to calculate the percentage of change (%SMHC) and recovery (%SMHR). As much the change (ΔZC) and recovery (ΔZR) percentage of mineral content were calculated. Next, fluoride present in enamel (mg F/mm3) and in solution the pH-cycling (mg F) were measured. Negative correlation was observed between %SMHC and mg F/mm3 (r=-0.9989; p=0.0000001), %SMHC and mg F (r=-0.9884; p=0.0000001), also between DZC and mg F/mm3 (r=- 0.9762; p=0.0048) and DZC and mg F (r=-0.9975; p=0.0000001); and positive between mg F/mm3 and mg F (r=0.9802; p=0.0018). There was positive correlation between %SMHR and mg F/mm3 (r=0.9770; p=0.004), %SMHR and mg F (r=0.9939; p=0.0000001), and also between mg F and mg F/mm3 (r=0.9819; p=0.0010). As per DZR, there was correlation with mg F/mm3 (r=0.9853; p=0.0002) and mg F (r=0.9975; p=0.0000001). The pH-cycling model was validated by verification of in vitro dose-response relationship of fluoride-releasing materials in demineralization and in remineralization of enamel. / Orientador: Denise Pedrini Ostini / Coorientador: Alberto Carlos Botazzo Delbem / Banca: Cleide Cristina Rodrigues Martinhon / Banca: Robson Frederico Cunha / Banca: Stella Kossatz Pereira / Banca: Salete Moura Bonifácio da Silva / Doutor

As hidroxiapatitas (HA) são amplamente utilizadas como biomateriais osteocondutores, mas não possuem propriedades osteoindutoras e osteogênicas. O fluoreto, por sua vez, quando presente no meio em doses adequadas (da ordem de 10-5 M), é capaz de aumentar a proliferação de osteoblastos e a atividade da fosfatase alcalina. Assim, o objetivo do presente estudo foi modificar um biomaterial existente, constituído por HA bifásica (70% HA + 30% &#x3B2;-TCP) porosa, pela adsorção de fluoreto. A capacidade de liberação de fluoreto deste material para meio de cultura osteogênico foi também avaliada. Foi ainda feita caracterização físicoquímica do material com fluoreto adsorvido, em comparação ao material original (FTIR, DRX e MEV). Para os ensaios de adsorção de fluoreto, soluções com diferentes concentrações deste elemento, na forma de NaF, foram adicionadas à HÁ bifásica na proporção de 10 g de HA por 50 mL de solução contendo fluoreto. Os testes foram feitos em duas etapas. Na primeira etapa, as concentrações de fluoreto empregadas variaram entre 100 e 2000 ppm e foi feita incubação por 3, 6, 18 ou 24 h, em temperatura ambiente, sob agitação constante. Após estes intervalos de tempo, removeu-se o sobrenadante e colocou-se o restante na estufa a 40oC, até a completa secagem dos grânulos. Os mesmos foram armazenados para posterior quantificação de fluoreto adsorvido, que foi feita com o eletrodo, após difusão facilitada por exametildisiloxano. Na segunda etapa, as concentrações de fluoreto empregadas variaram entre 0,625 e 80 ppm, sendo feita incubação por 24 ou 48 h. Para a avaliação da liberação de fluoreto da HA adsorvida, as amostras de HA com fluoreto adsorvido foram incubadas à temperatura ambiente com meio de cultura &#x3B1;-MEM, na proporção de 10 g de HA por 50 mL de meio, sob agitação, por 3, 6, ou 24 h e o sobrenadante foi coletado para quantificação de fluoreto. Foi observada uma relação dose- resposta entre a concentração de fluoreto que se adsorveu à HA e concentração de fluoreto presente nas soluções em que a HA foi incubada. O tempo de incubação nas soluções fluoretadas não alterou a concentração de fluoreto adsorvido (exceto para uma diminuição da adsorção para o tempo de 48 h). A porcentagem de adsorção de fluoreto variou entre 15 e 35%. Houve uma redução na concentração de fluoreto liberada para o meio, em função da redução da concentração de fluoreto na solução de incubação da HA. Liberações da ordem de 10-5 M foram observadas para a HA incubada por 24 h em 80 ppm fluoreto. A avaliação físico-química da HA bifásica porosa com fluoreto adsorvido revelou características semelhantes ao material original, sem fluoreto adsorvido. Em conclusão, a incubação da HA bifásica porosa em solução contendo 80 ppm de fluoreto por 24 horas é capaz de levar a uma adsorção de fluoreto tal que permite a liberação deste elemento na ordem de 10-5 M em meio de cultura osteogênico. Esta adsorção de fluoreto não altera as propriedades físico-químicas do material. / Hydroxyapatites (HA) are broadly employed as osteoconductive biomaterials, but they do not possess osteoinductive or osteogenic properties. Fluoride, when present in the environment in appropriate doses (around 10-5 M) is able to increase the proliferation of osteoblastos and the activity of alcaline phosphatase. Thus, the aim of the present study was to modify an existing biomaterial (biphasic HA, containing 70% HA and 30% &#x3B2;-TCP), through the adsorption of fluoride. The ability of this material to release fluoride for osteogenic culture medium was also evaluated. The biomaterial containing adsorbed fluoride was characterized physic-chemically (FTIR, DRX and SEM), in comparison to its counterpart without adsorbed fluoride. For the fluoride adsorption experiments, solutions with different fluoride concentrations (as NaF) were added to biphasic HA (10 g HA : 50 mL fluoridecontaining solution). Tests were carried out in 2 stages. In the first stage, fluoride concentrations used ranged between 100 and 2000 ppm. Incubation was done for 3, 6, 18 or 24 h, at room temperature, under constant agitation. After incubation, supernatant was removed and the pellets were allowed to dry at 40oC. The resulting material was stored for subsequent fluoride analysis that was done with the electrode, after examethyldisiloxane-facilitated diffusion. In the second stage, the fluoride concentrations ranged between 0.625 and 80 ppm and incubation was carried out for 24 or 48 h. For the evaluation of the release of adsorbed fluoride, samples of HA containing adsorbed fluoride were incubated in &#x3B1;-MEM medium at room temperature (10 g HA : 50 mL medium), under agitation, for 3, 6 or 24 h. Supernatant was collected for fluoride quantification. A dose- response relationship was observed between the concentration of fluoride that adsorbed to HA and the fluoride concentration in the incubation solutions. The time of incubation did not change the concentration of adsorbed fluoride (except for a reduction in adsorption for 48 h). The percentage of fluoride adsorption ranged between 15 and 35%. It was observed a reduction in the concentration of fluoride that was released to the medium, as a function of the reduction of the fluoride concentration in the incubation solution. Fluoride releases around 10-5 M were observed for HA incubated with 80 ppm fluoride for 24 h. Physico-chemical evaluation of the porous biphasic HA containing adsorbed fluoride revealed a pattern similar to the one observed for the original material (without adsorbed fluoride). In conclusion, the incubation of porous biphasic HA in a solution containing 80 ppm fluoride for 24 h allows adsorption of F to HA to an extent that allows the release of 10-5 M fluoride concentrations to the medium. In addition, fluoride adsorption to HA does not change the physico-chemical properties of the material.

Made available in DSpace on 2014-10-09T12:49:05Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:10:00Z (GMT). No. of bitstreams: 1 09676.pdf: 487919 bytes, checksum: 0745fbc8dd8d4e9f050ed47878924b0a (MD5) / Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia) / IPEN/D-MPLO / Instituto de Pesquisas Energeticas e Nucleares, IPEN/CNEN-SP; Faculdade de Odontologia, Universidade de Sao Paulo

Orientadores: Giselle Maria Marchi Baron, Carlos Eduardo Francci / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-12T16:01:12Z (GMT). No. of bitstreams: 1 Lobo_MaristelaMaia_D.pdf: 970564 bytes, checksum: cceba3a37b5226f311ffa842569a6760 (MD5) Previous issue date: 2008 / Resumo: Este estudo clínico randomizado e duplo-cego avaliou os efeitos do fluoreto de sódio, presente na composição do gel clareador (0,11%) e/ou aplicado topicamente em moldeira (2%), sobre a sensibilidade dentinária, a saúde gengival e a satisfação de pacientes submetidos ao clareamento dental caseiro com peróxido de carbamida a 10%. Sessenta voluntários foram, aleatoriamente, divididos em seis grupos (n=10): (G1) gel de peróxido de carbamida a 10%+ gel de flúor a 2%; (G2) gel de peróxido de carbamida a 10% + placebo do gel de flúor a 2%; (G3) placebo do gel clareador + gel de flúor a 2%; (G4) placebo do gel clareador + placebo do gel de flúor a 2%; (G5) gel de peróxido de carbamida a 10% contendo 0,11% de fluoreto de sódio + gel de flúor a 2%; (G6) gel de peróxido de carbamida a 10% contendo 0,11% de fluoreto de sódio + placebo do gel de flúor a 2%. Esses voluntários trataram seus dentes durante a noite por, no mínimo, 4 horas, durante 14 dias consecutivos. Após cada jornada de clareamento, eles aplicavam o gel de flúor (ativo ou placebo) na moldeira por 5 minutos. Na consulta de baseline, 7, 14, 21 e 28 dias após o início do clareamento, foram avaliados: sensibilidade a estímulos tátil e evaporativo (através de escala analógica visual de dor), satisfação do voluntário (através de questionário, nos retornos de 7 e 14 dias), e parâmetros periodontais (após 14 e 28 dias). Do total de voluntários avaliados, 47,36% demonstraram sensibilidade ao estímulo evaporativo e 17,54% ao estímulo tátil, sem diferença estatística entre os grupos. A satisfação positiva para este tratamento foi de 61,4%. Houve uma significativa diminuição da profundidade de sondagem avaliada no retorno de 14 dias, e não houve diferença estatística entre os grupos com relação ao índice de sangramento. Pode-se concluir que o flúor, nas concentrações avaliadas, não foi capaz de evitar ou diminuir a ocorrência de sensibilidade associada ao clareamento dental caseiro com peróxido de carbamida a 10%. / Abstract: This double-blind and randomized clinical trial evaluated the effects of sodium fluoride - within the composition of bleaching gel (0,11%) or topically applied (2%) - over dentin hypersensitivity, gingival health and overall satisfaction of patients submitted to 10% carbamide peroxide nightguard vital bleaching. Sixty volunteers were randomly assigned to six groups (n=10): (G1) 10% carbamide peroxide gel + 2% neutral fluoride gel; (G2) 10% carbamide peroxide gel + placebo fluoride gel; (G3) placebo bleaching gel + 2% neutral fluoride gel; (G4) placebo bleaching gel + placebo fluoride gel; (G5) 10% carbamide peroxide gel with 0,11% sodium fluoride + 2% neutral fluoride gel; (G6) 10% carbamide peroxide gel with 0,11% sodium fluoride + placebo fluoride gel. Treatment was conducted for 14 consecutive days, and after each night of bleaching volunteers wore trays with topic fluoride gels (active or placebo) for 5 minutes. At baseline and after 7, 14, 21 and 28 days from the beginning of treatment, were evaluated: dentin sensitivity to tactile and evaporative stimuli (using analogue VAS scale), volunteer satisfaction (applying questionnaire at recalls 7 and 14), and periodontal health (at recalls 14 and 28). From the total of volunteers evaluated, 47.36% demonstrated evaporative sensitivity and 17.54% tactile sensitivity, with no statistical difference between groups. Positive satisfaction achieved 61.4%, with a mean bleaching of three tons of Vita scale for active groups and no influence of fluoride. Probing depth was lower at second recall (day 14), but there was no statistical difference for bleeding on probing between groups. In conclusion, different concentrations of sodium fluoride were not capable of preventing or diminishing dentin sensitivity during 10% carbamide peroxide nightguard vital bleaching. / Doutorado / Dentística / Doutor em Clínica Odontológica

Orientadores: Jaime Aparecido Cury, Lívia Maria Andaló Tenuta / Dissertação (mestrado profissional) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-25T17:25:07Z (GMT). No. of bitstreams: 1 Caldarelli_PabloGuilherme_M.pdf: 1213004 bytes, checksum: ce7cfda4a643871aef7cc435ab6da7f8 (MD5) Previous issue date: 2014 / Resumo: A escovação dental com dentifrícios fluoretados é considerada além do meio mais racional de uso de fluoretos como um dos fatores responsáveis pelo declínio da cárie dentária ocorrido no Brasil e no mundo. Revisões sistemáticas da literatura mostram evidências que para um dentifrício ter atividade anticárie ele deve conter uma concentração de pelo menos 1000 ppm de flúor, o qual por princípio deve estar solúvel. As normas brasileiras sobre a agregação de fluoreto aos dentifrícios sofreram mudanças desde 1989, fazendo com que o potencial anticárie desses produtos não esteja sendo assegurado pela regulamentação vigente. Assim, o objetivo deste estudo foi realizar uma análise crítica com relação à necessidade de revisão da atual Resolução da Agência Nacional de Vigilância Sanitária (ANVISA), de 28 de agosto de 2000, tendo em vista que parâmetros mínimos para assegurar que um dentifrício mantenha sua concentração de flúor com atividade anticárie (quimicamente solúvel) até seu prazo de validade não estão contemplados na referida norma. Ela apenas estabelece o máximo de fluoreto total (0,15%) que um dentifrício deve conter, podendo estar ele totalmente insolúvel (inativo contra cáries). Para isso, foi realizada uma busca na literatura sobre a concentração de flúor encontrada nos dentifrícios utilizados no Brasil. Com base nas publicações encontradas foi feita uma discussão sobre a necessidade de adequação da atual resolução da ANVISA. Concluiu-se que nem todos os dentifrícios brasileiros são capazes de manter até seu prazo de validade a concentração mínima de 1000 ppm F para terem potencial efeito anticárie, justificando a necessidade de revisão da regulamentação vigente / Abstract: Toothbrushing with fluoride toothpaste is considered as the most rational way of fluoride use and also as one of the factors responsible for dental caries decline in Brazil and worldwide. Systematic literature reviews show evidences that to have anticaries activity toothpastes must contain a concentration of at least 1000 ppm fluoride, which should be soluble. Brazilian regulations about fluoride toothpaste have changed since 1989 and the anticaries potential of these products is not being guaranteed by the current regulation. Thus, the aim of this study was to conduct a critical analysis regarding the need to revise the current Brazilian resolution, because it does not ensure minimum requirements for that a dentifrice maintains till its expire date fluoride concentration with anticaries activity (chemically soluble). It only sets the maximum total fluoride (0.15%) that a toothpaste may contain, which may be totally insoluble (inactive against cavities). For this, it was made a literature search about the concentration of fluoride found in toothpaste used in Brazil. Based on publications found, it was made a discussion on the need to review the current ANVISA resolution. It was concluded that not all Brazilian toothpastes are able to maintain until theirs expiry date the minimum concentration of 1,000 ppm F to have anticaries potential, justifying the need to review the current Brazilian guidelines about dentifrices / Mestrado / Odontologia em Saude Coletiva / Mestre em Odontologia em Saúde Coletiva

Routes to sterically demanding organofluorine-containing phosphines are described, and the stereoelectronic properties and chemistry of the resulting new ligands investigated. The synthesis of Cy2P(CF=CF2), 3, has been accomplished. The nucleophilic substitution of Ph2P(CF=CF2) with tBuLi produces the (Z)-isomer, Ph2P(Z-CF=CF(tBu)), 5-(Z), predominantly, which has been shown to be less electron-withdrawing than Ph2P(CF=CF2), and similar in size to 3. The bis-trifluoropropynyl substituted phosphine PhP(tfp)2, 7, has been prepared, and its reaction with tBuLi investigated. This results in the formation of three previously unknown species, the gem¬-difluorocyclopropenyl-containing compound, PhtBuP(dfcp), 8, (Z)-Ph2P(CH=C(t¬Bu)CF3), 9, and PhtBuP(tfp), 10. The nucleophilic substitution occurs preferentially at the phosphorus centre, as shown by the reaction with one equivalent of tBuLi at -60°C, where compounds 9 and 10 are formed. A new route to perfluoroalkyl-containing phosphines has been discovered. The addition of a perfluoroalkyl iodide to Ph2PSiMe3 results in the formation of six new phosphines, and has been shown to be extendable to partially fluorinated systems. The route can also be applied to iPr2PSiMe3, and to the chiral phosphine PhMePSiMe3. Three examples, Ph2PRf (Rf = CF(CF3)2, 15, (sC4F¬9), 18, (cyc-C6F11), 19), have been produced on a preparative scale. The reaction of the bis-trimethylsilyl phenyl phosphine with (CF3)2CFI has been investigated, though it does not result in the production of the bis-perfluoroalkyl-substituted phosphine, instead the previously unknown P-chiral compound, PhP(H)CF(CF3)2, 27 is formed. Mechanistic studies have indicated that Ph2P-PPh2 is the intermediate, and that there is no evidence of a radical mechanism. There is no reaction between Me2(S)P-P(S)Me2 and (CF3)2CFI, though there is when Me2P-P(S)Me2 is used, suggesting that the lone pair of the intermediate diphosphine is necessary for the reaction to proceed. This has resulted in the formation of the new compound, Me2PCF(CF3)2, 28. The chemistry of the perfluoroalkyl-containing phosphines has been investigated; they do not quaternise, but are oxidatively sensitive. The phosphorus(V) selenides of 15, 18, and 19 have been prepared, and based on their 1JPSe coupling constants, the perfluoroalkyl-groups impart a greater electron-withdrawing effect than perfluorovinyl, trifluoropropynyl, or alkoxy fragments. The oxidation of 15 and 18 with XeF2 has also been accomplished, and shown to yield the corresponding F2PPh2Rf compounds. The molybdenum(0) pentacarbonyl complexes of 3, 7, and 15 have been synthesised and perfluoroalkyl-groups have again been shown to be more electron-withdrawing than perfluorovinyl and trifluoropropynyl groups by comparison of v(CO) values. The gold(I) chloride complexes of Ph2PCF3, 15, and 18 and the platinum(II) dichloride complexes of 3 and 15 have been prepared, and the size of these ligands has been estimated from the crystal structures. Compound 18 has been shown to be the largest of these compounds, with a cone angle of 187°.