In vitro antioxidant activity and in vivo efficacy of topical formulations containing vitamin C and its derivatives studied by non-invasive methods

Background/purpose: Vitamins C and its derivatives, mainly due to their antioxidant properties, are being used in cosmetic products to protect and to reduce the signs of ageing. However, there are no studies comparing the effects of vitamin C [ascorbic acid (AA)] and its derivatives, magnesium ascorbyl phosphate (MAP) and ascorbyl tetra-isopalmitate (ATIP), when vehiculated in topical formulations, mainly using objective measurements, which are an important tool in clinical efficacy studies. Thus, the objective of this study was to determine the in vitro antioxidant activity of AA and its derivatives, MAP and ATIP, as well as their in vivo efficacy on human skin, when vehiculated in topical formulations. Methods: The study of antioxidant activity in vitro was performed with an aqueous and a lipid system. The in vivo methodology consisted of the application of these formulations on human volunteers` forearm skin and the analysis of the skin conditions after 4-week period daily applications in terms of transepidermal water loss (TEWL), stratum corneum moisture content and viscoelasticity using a Tewameter (R), Corneometer (R) and Cutometer (R), respectively. Results: In vitro experiments demonstrated that in an aqueous system, AA had the best antioxidant potential, and MAP was more effective than ATIP, whereas in the lipid system ATIP was more effective than MAP. In in vivo studies, all formulations enhanced stratum corneum moisture content after a 4-week period daily applications when compared with baseline values; however, only the formulation containing AA caused alterations in TEWL values. The formulations containing MAP caused alterations in the viscoelastic-to-elastic ratio, which suggested its action in the deeper layers of the skin. Conclusion: AA and its derivates presented an in vitro antioxidant activity but AA had the best antioxidant effect. In in vivo efficacy studies, only the formulation containing AA caused alterations in TEWL values and the formulation containing MAP caused alterations in the viscoelastic-to-elastic ratio. This way, vitamin C derivatives did not present the same effects of AA on human skin; however, MAP showed other significant effect-improving skin hydration, which is very important for the normal cutaneous metabolism and also to prevent skin alterations and early ageing.

Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic periodontal disease and decrease after non-surgical periodontal therapy

Background: Periodontal disease shares risk factors with cardiovascular diseases and other systemic inflammatory diseases. The present study was designed to assess the circulating matrix metalloproteinases (MMPs) from chronic periodontal disease patients and, subsequently, after periodontal therapy. Methods: We compared the plasma concentrations of MMP-2. MMP-3, MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, and total gelatinolytic activity in patients with periodontal disease (n =28) with those of control subjects (n = 22) before and 3 months after non-surgical periodontal therapy. Results: Higher plasma MMP-3, MMP-8, and MMP-9 concentrations were found in periodontal disease patients compared with healthy controls (all P<0.05), whereas MMP-2, TIMP-1, and TIMP-2 levels were not different. Treatment decreased plasma MMP-8 and MMP-9 concentrations by 35% and 39%, respectively (both P<0.02), while no changes were found in controls. MMP-2, MMP-3, TIMP-1, and TIMP-2 remained unaltered in both groups. Plasma gelatinolytic activity was higher in periodontal disease patients compared with controls (P<0.001) and decreased after periodontal therapy (P<0.05). Conclusions: This study showed increased circulating MMP-8 and MMP-9 levels and proteolytic activity in periodontal disease patients that decrease after periodontal therapy. The effects of periodontal therapy suggest that it may attenuate inflammatory chronic diseases. (C) 2009 Published by Elsevier B.V.

Deconstructing Tick Saliva NON-PROTEIN MOLECULES WITH POTENT IMMUNOMODULATORY PROPERTIES

Dendritic cells (DCs) are powerful initiators of innate and adaptive immune responses. Ticks are blood-sucking ectoparasite arthropods that suppress host immunity by secreting immunomodulatory molecules in their saliva. Here, compounds present in Rhipicephalus sanguineus tick saliva with immunomodulatory effects on DC differentiation, cytokine production, and costimulatory molecule expression were identified. R. sanguineus tick saliva inhibited IL-12p40 and TNF-alpha while potentiating IL-10 cytokine production by bone marrow-derived DCs stimulated by Toll-like receptor-2, -4, and -9 agonists. To identify the molecules responsible for these effects, we fractionated the saliva through microcon filtration and reversed-phase HPLC and tested each fraction for DC maturation. Fractions with proven effects were analyzed by micro-HPLC tandem mass spectrometry or competition ELISA. Thus, we identified for the first time in tick saliva the purine nucleoside adenosine (concentration of similar to 110pmol/mu l) as a potent anti-inflammatory salivary inhibitor of DC cytokine production. We also found prostaglandin E(2) (PGE(2) similar to 100 nM) with comparable effects in modulating cytokine production by DCs. Both Ado and PGE(2) inhibited cytokine production by inducing cAMP-PKA signaling in DCs. Additionally, both Ado and PGE(2) were able to inhibit expression of CD40 in mature DCs. Finally, flow cytometry analysis revealed that PGE(2), but not Ado, is the differentiation inhibitor of bone marrow-derived DCs. The presence of non-protein molecules adenosine and PGE(2) in tick saliva indicates an important evolutionary mechanism used by ticks to subvert host immune cells and allow them to successfully complete their blood meal and life cycle.

The attentional demands of preferred and non-preferred gait patterns

The purpose of this study was to determine the attentional demands of natural and imposed gait, as well as the attentional costs of transitions between the walking and running co-ordination patterns. Seven healthy young men and four healthy young women undertook an auditory probe reaction time task concurrently with self-selected gait (Experiment 1) and imposed walking and running (Experiment 2) at different speeds on a motor-driven treadmill. In Experiment 1, where participants were free to choose their own movement pattern to match the speed of travel of the treadmill, normal gait control was shown to have a significant attentional cost, and hence not be automatic in the classical sense. However, this attentional cost did not differ between the two gait modes or at the transition point. In Experiment 2, where participants were required to maintain specific gait modes regardless of the treadmill speed, the maintenance of walking at speeds normally associated with running was found to have an attentional cost whereas this was not the case for running at normal walking speeds. Collectively the findings support a model of gait control in which the normal switching between gait modes is determined with minimal attention demand and in which it is possible to sustain non-preferred gait modes although, in the case of walking, only at a significant attentional/cognitive cost. © 2002 Elsevier Science B.V. All rights reserved.

Children’s respiratory health and daily particulate levels in ten non-urban communities

We conducted a study to assess the association between the acute respiratory health of children and the levels of particulates in communities near and away from active opencast coal mines. The study enrolled children aged 1–11 years from the general population of five socioeconomically matched pairs of nonurban communities in northern England. Diaries of respiratory events were collected for 1405 children, and information was collected on the consultations of 2442 children with family/general practitioners over the 6-week study periods during 1996–1997, with concurrent monitoring of particulate levels. The associations found between daily PM10 levels and respiratory symptoms were frequently small and positive and sometimes varied between communities. The magnitude of these associations were in line with those from previous studies, even though daily particulate levels were low, and the children were drawn from the general population, rather than from the population with respiratory problems. The associations among asthma reliever use, consultations with general practitioners, and daily particulate levels were of a similar strength but estimated less precisely. The strength of association between all respiratory health measures and particulate levels was similar in communities near and away from opencast coal mining sites.

Exact solution of the A(n-1)((1)) trigonometric vertex model with non-diagonal open boundaries

The A(n-1)((1)) trigonometric vertex model with generic non-diagonal boundaries is studied. The double-row transfer matrix of the model is diagonalized by algebraic Bethe ansatz method in terms of the intertwiner and the corresponding face-vertex relation. The eigenvalues and the corresponding Bethe ansatz equations are obtained.

Non-Equilibrium Reaction Rates in the Macroscopic Chemistry Method for DSMC Calculations

The Direct Simulation Monte Carlo (DSMC) method is used to simulate the flow of rarefied gases. In the Macroscopic Chemistry Method (MCM) for DSMC, chemical reaction rates calculated from local macroscopic flow properties are enforced in each cell. Unlike the standard total collision energy (TCE) chemistry model for DSMC, the new method is not restricted to an Arrhenius form of the reaction rate coefficient, nor is it restricted to a collision cross-section which yields a simple power-law viscosity. For reaction rates of interest in aerospace applications, chemically reacting collisions are generally infrequent events and, as such, local equilibrium conditions are established before a significant number of chemical reactions occur. Hence, the reaction rates which have been used in MCM have been calculated from the reaction rate data which are expected to be correct only for conditions of thermal equilibrium. Here we consider artificially high reaction rates so that the fraction of reacting collisions is not small and propose a simple method of estimating the rates of chemical reactions which can be used in the Macroscopic Chemistry Method in both equilibrium and non-equilibrium conditions. Two tests are presented: (1) The dissociation rates under conditions of thermal non-equilibrium are determined from a zero-dimensional Monte-Carlo sampling procedure which simulates ‘intra-modal’ non-equilibrium; that is, equilibrium distributions in each of the translational, rotational and vibrational modes but with different temperatures for each mode; (2) The 2-D hypersonic flow of molecular oxygen over a vertical plate at Mach 30 is calculated. In both cases the new method produces results in close agreement with those given by the standard TCE model in the same highly nonequilibrium conditions. We conclude that the general method of estimating the non-equilibrium reaction rate is a simple means by which information contained within non-equilibrium distribution functions predicted by the DSMC method can be included in the Macroscopic Chemistry Method.

Finite element analysis of steady-state natural convection problems in fluid-saturated porous media heated from below

In this paper, a progressive asymptotic approach procedure is presented for solving the steady-state Horton-Rogers-Lapwood problem in a fluid-saturated porous medium. The Horton-Rogers-Lapwood problem possesses a bifurcation and, therefore, makes the direct use of conventional finite element methods difficult. Even if the Rayleigh number is high enough to drive the occurrence of natural convection in a fluid-saturated porous medium, the conventional methods will often produce a trivial non-convective solution. This difficulty can be overcome using the progressive asymptotic approach procedure associated with the finite element method. The method considers a series of modified Horton-Rogers-Lapwood problems in which gravity is assumed to tilt a small angle away from vertical. The main idea behind the progressive asymptotic approach procedure is that through solving a sequence of such modified problems with decreasing tilt, an accurate non-zero velocity solution to the Horton-Rogers-Lapwood problem can be obtained. This solution provides a very good initial prediction for the solution to the original Horton-Rogers-Lapwood problem so that the non-zero velocity solution can be successfully obtained when the tilted angle is set to zero. Comparison of numerical solutions with analytical ones to a benchmark problem of any rectangular geometry has demonstrated the usefulness of the present progressive asymptotic approach procedure. Finally, the procedure has been used to investigate the effect of basin shapes on natural convection of pore-fluid in a porous medium. (C) 1997 by John Wiley & Sons, Ltd.

Molecular cocrystals of carboxylic acids. XXVII - An investigation into the use of triphenylphosphine oxide cocrystals for non-linear optics: the crystal structure of the adduct of triphenylphosphine oxide with N-methylpyrrole-2-carboxylic acid

Four adducts of triphenylphosphine oxide with aromatic carboxylic acids have been synthesized and tested for second-order non-linear optical properties. These were with N-methylpyrrole-2-carboxylic acid (I), indole-2-carboxylic acid (2), 3-dimethylaminobenzoic acid (3), and thiophen-2-carboxylic acid (4). Compound (1) produced clear, colourless crystals (space group P2(1)2(1)2(1) With a 9.892(1), b 14.033(1), c 15.305(1) Angstrom, Z 4) which allowed the structure to be determined by X-ray diffraction.

Medication prescribing and administration in nursing homes

Objective: to examine the key determinants of pharmaco-epidemiology in Australian nursing homes. Design: a cross-sectional survey of medication use in 998 residents in 15 nursing homes in Southern Queensland and Northern New South Wales, Results: the total, laxative, digoxin/diuretic, benzodiazepine and psycholeptic medication prescribed and administered to residents of nursing homes was affected to differing extents by age and gender, the nursing home, resident functional disability and medical practitioner. Resident Classification Instrument (RCI) category and nursing home were the dominant determinants for prescribing and administration of the total drugs, laxative, benzodiazepine and psycholeptic medications. In contrast, the resident use of digoxin and/or diuretics was dependent on the resident age and on the functional disability (RCI category) of the resident but not medical practitioner or nursing home. Approximately 30% of medications were prescribed on a pro re nata (p.r.n.) basis and administered at the discretion of registered nurses. Conclusion: nursing home culture is a major determinant of the variability in medication use between residents, particularly for those medications often prescribed for p.r.n. use. The nursing home does not account for variation in the use of digoxin and/or diuretics which are prescribed on a non-discretionary basis.

Comparative labor market performance of visaed and non-visaed migrants: Pacific islanders in Sydney

Using survey data for Tongan and Samoan migrants in Sydney the effects of visa restrictions on labor market performance of migrants are assessed. Univariate analysis suggests a positive association between unemployment and the unrestricted entry of Samoan step-migrants from New Zealand. A probit model of the determinants of unemployment is estimated with controls for human capital and demographic variables. While human capital endowments are important, visa restrictions do not have a significant effect on either group's employability. Implications for policy are discussed highlighting the complementarities between host country immigration policies and foreign aid programs.

Determination of pore size distributions by regularization and finite element collocation

The problem of extracting pore size distributions from characterization data is solved here with particular reference to adsorption. The technique developed is based on a finite element collocation discretization of the adsorption integral, with fitting of the isotherm data by least squares using regularization. A rapid and simple technique for ensuring non-negativity of the solutions is also developed which modifies the original solution having some negativity. The technique yields stable and converged solutions, and is implemented in a package RIDFEC. The package is demonstrated to be robust, yielding results which are less sensitive to experimental error than conventional methods, with fitting errors matching the known data error. It is shown that the choice of relative or absolute error norm in the least-squares analysis is best based on the kind of error in the data. (C) 1998 Elsevier Science Ltd. All rights reserved.

Phosphorylation of the C-terminal sites of human p53 reduces non-sequence-specific DNA binding as modeled with synthetic peptides

Phosphorylation of the tumor suppressor p53 is generally thought to modify the properties of the protein in four of its five independent domains. We used synthetic peptides to directly study the effects of phosphorylation on the non-sequence-specific DNA binding and conformation of the C-terminal, basic domain. The peptides corresponded to amino acids 361-393 and were either nonphosphorylated or phosphorylated at the protein kinase C (PKC) site, Ser378, or the casein kinase II (CKII) site, Ser392, or bis-phosphorylated on both the PKC and the CKII sites. A fluorescence polarization analysis revealed that either the recombinant p53 protein or the synthetic peptides bound to two unrelated target DNA fragments. Phosphorylation of the peptide at the PKC or the CKII sites clearly decreased DNA binding, and addition of a second phosphate group almost completely abolished binding. Circular dichroism spectroscopy showed that the peptides assumed identical unordered structures in aqueous solutions. The unmodified peptide, unlike the Ser378 phosphorylated peptide, changed conformation in the presence of DNA. The inherent ability of the peptides to form an alpha-helix could be detected when circular dichroism and nuclear magnetic resonance spectra were: taken in trifluoroethanol-water mixtures. A single or double phosphorylation destabilized the helix around the phosphorylated Ser378 residue but stabilized the helix downstream in the sequence.

Evolution of three-dimensional folds for a non-Newtonian plate in a viscous medium

We derive analytical solutions for the three-dimensional time-dependent buckling of a non-Newtonian viscous plate in a less viscous medium. For the plate we assume a power-law rheology. The principal, axes of the stretching D-ij in the homogeneously deformed ground state are parallel and orthogonal to the bounding surfaces of the plate in the flat state. In the model formulation the action of the less viscous medium is replaced by equivalent reaction forces. The reaction forces are assumed to be parallel to the normal vector of the deformed plate surfaces. As a consequence, the buckling process is driven by the differences between the in-plane stresses and out of plane stress, and not by the in-plane stresses alone as assumed in previous models. The governing differential equation is essentially an orthotropic plate equation for rate dependent material, under biaxial pre-stress, supported by a viscous medium. The differential problem is solved by means of Fourier transformation and largest growth coefficients and corresponding wavenumbers are evaluated. We discuss in detail fold evolutions for isotropic in-plane stretching (D-11 = D-22), uniaxial plane straining (D-22 = 0) and in-plane flattening (D-11 = -2D(22)). Three-dimensional plots illustrate the stages of fold evolution for random initial perturbations or initial embryonic folds with axes non-parallel to the maximum compression axis. For all situations, one dominant set of folds develops normal to D-11, although the dominant wavelength differs from the Biot dominant wavelength except when the plate has a purely Newtonian viscosity. However, in the direction parallel to D-22, there exist infinitely many modes in the vicinity of the dominant wavelength which grow only marginally slower than the one corresponding to the dominant wavelength. This means that, except for very special initial conditions, the appearance of a three-dimensional fold will always be governed by at least two wavelengths. The wavelength in the direction parallel to D-11 is the dominant wavelength, and the wavelength(s) in the direction parallel to D-22 is determined essentially by the statistics of the initial state. A comparable sensitivity to the initial geometry does not exist in the classic two-dimensional folding models. In conformity with tradition we have applied Kirchhoff's hypothesis to constrain the cross-sectional rotations of the plate. We investigate the validity of this hypothesis within the framework of Reissner's plate theory. We also include a discussion of the effects of adding elasticity into the constitutive relations and show that there exist critical ratios of the relaxation times of the plate and the embedding medium for which two dominant wavelengths develop, one at ca. 2.5 of the classical Biot dominant wavelength and the other at ca. 0.45 of this wavelength. We propose that herein lies the origin of parasitic folds well known in natural examples.