AVALIAÇÃO COMPARATIVA ENTRE AGRADABILIDADE FACIAL, PROPORÇÃO ÁUREA E PADRÃO FACIAL

O propósito desta pesquisa foi estudar algumas análises faciais utilizadas para diagnóstico ortodôntico e verificar a concordância entre norma lateral e frontal na avaliação da agradabilidade facial para os grupos leigos e profissionais, a concordância entre estes grupos na avaliação da agradabilidade facial nas normas lateral e frontal, bem como verificar a associação entre agradabilidade facial e Proporção Áurea, agradabilidade facial e Padrão Facial e entre Padrão Facial e Proporção Áurea. Utilizou-se 208 fotografias faciais padronizadas (104 laterais e 104 frontais) de 104 indivíduos escolhidos aleatoriamente, que primeiramente foram classificadas em agradável , aceitável e desagradável por dois grupos distintos: grupo Ortodontia e grupo Leigos . As fotografias laterais e frontais foram submetidas a medidas de Proporção Áurea Facial por meio de programa computadorizado e os indivíduos foram classificados quanto ao Padrão Facial pelo seu aspecto lateral. Após análise estatística, verificou-se que não houve concordância entre as variáveis da avaliação de agradabilidade estudadas, bem como não houve associação entre Proporção Áurea com agradabilidade facial ou com Padrão Facial. Entre agradabilidade facial e Padrão Facial, observou-se para a norma lateral associação fortemente positiva, porém para a frontal não houve associação para ambos os grupos de avaliadores.

Flexibility of short-strand RNA in aqueous solution as revealed by molecular dynamics simulation:are A′-RNA and A-RNA distinct conformational structures?

We use molecular dynamics simulations to compare the conformational structure and dynamics of a 21-base pair RNA sequence initially constructed according to the canonical A-RNA and A'-RNA forms in the presence of counterions and explicit water. Our study aims to add a dynamical perspective to the solid-state structural information that has been derived from X-ray data for these two characteristic forms of RNA. Analysis of the three main structural descriptors commonly used to differentiate between the two forms of RNA namely major groove width, inclination and the number of base pairs in a helical twist over a 30 ns simulation period reveals a flexible structure in aqueous solution with fluctuations in the values of these structural parameters encompassing the range between the two crystal forms and more. This provides evidence to suggest that the identification of distinct A-RNA and A'-RNA structures, while relevant in the crystalline form, may not be generally relevant in the context of RNA in the aqueous phase. The apparent structural flexibility observed in our simulations is likely to bear ramifications for the interactions of RNA with biological molecules (e.g. proteins) and non-biological molecules (e.g. non-viral gene delivery vectors). © CSIRO 2009.

Bile-salt-induced aggregation of poly(N-isopropylacrylamide) and lowering of the lower critical solution temperature in aqueous solutions

The effect of sodium cholate (NaC; concentration 1-16 mM), a biological surfactant, on the aggregation behavior of 1% (w/v, 2.2 × 10(-3) M) poly(N-isopropylacrylamide) (PNIPAM) aqueous solutions was studied as a function of temperature. From turbidity, dynamic light scattering, viscosity, and fluorescence measurements, it was observed that (i) there is NaC-induced nanoscale aggregation of PNIPAM in its sol state and (ii) the lower critical solution temperature corresponding to sol-gel transition shifts to a lower temperature by about 2 °C.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

Mass transfer characteristics of two-aqueous-phase liquid-liquid mixtures

Mass transfer rates were studied using the falling drop method. Cibacron Blue 3 GA dye was the transferring solute from the salt phase to the PEG phase. Measurements were undertaken for several concentrations of the dye and the phase-forming solutes and with a range of different drop sizes, e.g. 2.8, 3.0 and 3.7 mm. The dye was observed to be present in the salt phase as finely dispersed solids but a model confirmed that the mass transfer process could still be described by an equation based upon the Whitman two-film model. The overall mass transfer coefficient increased with increasing concentration of the dye. The apparent mass transfer coefficient ranged from 1 x 10-5 to 2 x 10 -4 m/s. Further experiments suggested that mass transfer was enhanced at high concentration by several mechanisms. The dye was found to change the equilibrium composition of the two phases, leading to transfer of salt between the drop and continuous phases. It also lowered the interfacial tension (i.e. from 1.43 x 10-4 N/m for 0.01% w/w dye concentration to 1.07 x 10-4 N/m for 0.2% w/w dye concentration) between the two phases, which could have caused interfacial instabilities (Marangoni effects). The largest drops were deformable, which resulted in a significant increase in the mass transfer rate. Drop size distribution and Sauter mean drop diameter were studied on-line in a 1 litre agitated vessel using a laser diffraction technique. The effects of phase concentration, dispersed phase hold-up and impeller speed were investigated for the salt-PEG system. An increase in agitation speed in the range 300 rpm to 1000 rpm caused a decrease in mean drop diameter, e.g. from 50 m to 15 m. A characteristic bimodal drop size distribution was established within a very short time. An increase in agitation rate caused a shift of the larger drop size peak to a smaller size.

Ruthenium complexes as potential aqueous romp catalysts

The research described herein relates to studies into the Aqueous Ring-Opening Metathesis Polymerisation (ROMP) of bicyclic monomers using ruthenium complex catalysts. Two monomers were synthesised for the purpose of these studies, namely exo, exo-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid (7-oxanorbornenedicarboxylic acid) and exo, exo-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid (norbornene dicarboxylic acid). A number of ruthenium complexes were synthesised, amongst them a novel complex containing the water soluble phosphine ligand trist(hydroxymethyl)phosphine P(CH2OH)3. Its synthesis and characterisation are described and its physical properties compared and contrasted to analogous compounds of platinum and palladium. Its peculiar properties are ascribed to a trans-placement of the phosphine ligands. Dilatometry was investigated as a technique for the acquisition of kinetic data from aqueous metathesis reactions. For the attempted polymerisation of 7-oxanorbonenedicarboxylic acid the results are explained in terms of a reverse Diels-Alder reaction of the monomer. The reaction between Ru(CO)Cl2(H2O) and 7-oxanorbonenedicarboxylic acid was monitored using UV/Vis spectrometry and kinetic data retrieved. The data are explained in terms of a two stage reaction consisting of consecutive first order processes.The reaction between 7-oxanorbornenedicarboxylic acid and Ru(CO)Cl2(H2O) or Ru(P(CH2OH)3)3Cl2 was found to produce fumaric acid as one of the major products. This reaction is previously unreported in the literature and a mechanism is proposed.

Steric stabilization and dissolution characteristics of aqueous suspensions of pharmaceutical interest

The adsorption of two qroups of nonionic surface active agents and a series of hiqh molecular weiqht hydrophilic polymer fractions onto a polystyrene latex and a drug substance diloxanide furoate B.P. has been investigated. The presence of pores within the drug surface has been demonstrated and this is shown to increase the adsorption of low molecular weight polymer species. Differences in the maximum amount of polymer adsorbed at both solid-solution interfaces have been ascribed to the different hydrophobicities of the surface as determined by contact angle measurements. Adsorbed layer thicknesses of polymer on polystyrene latex have been determined by three techniques: microelectrophoresis, intensity fluctuation spectroscopy and by viscometric means. These results, in combination with adsorption data, were used to interpret the configuration of the adsorbed polymer molecules at the interface. The type of druq suspension produced on adsorbing the different polymers in the absence of electrostatic stabilization was correlated with theoretical prediuctions of suspension characteristics deduced from potential energy diagrams, The agreement was good for the adsorption of short chain length surfactants, but for the polyvinylalcohols, discrepancies were found between experiment and theory. This was attributed to the inappropriate use of a mean segment density approximation within the adsorbed layer to calculate attractive potentials between particles. A maximum in the redispersibility values for suspensions coated with adsorbed nonylphenylethoxylates was attributed to "partial static stabilization" of the particles in conjunction with the attractive forces operating in the sediment between bare surface patches on neighbouring particles. No significant change in the dissolution of the drug was observed when nonylphenylethoxylates were adsorbed due to desorption upon contact with the dissolution medium. Pluronic F68 and all the polyvinylalcohol fractions caused a reduction in the dissolution rate which is explained by the decreased diffusion of drug' through the adsorbed polymer layer.