Protein–phenolic interactions and inhibition of glycation – combining a systematic review and experimental models for enhanced physiological relevance

Background: While antiglycative capacity has been attributed to (poly)phenols, the exact mechanism of action remains unclear. Studies so far are often relying on supra-physiological concentrations and use of non-bioavailable compounds.<p></p> Methods: To inform the design of a physiologically relevant in-vitro study, we carried out a systematic literature review of dietary interventions reporting plasma concentrations polyphenol metabolites. Bovine Serum Albumin (BSA) was pre-treated prior to in vitro glycation: either no treatment (native), pre-oxidised (incubated with 10nM H2O2, for 8 hours) or incubated with a mixture of phenolic acids at physiologically relevant concentrations, for 8 hours). In-vitro glycation was carried out in presence of i) glucose only (0, 5 or 10mM), ii) glucose (0, 5 or 10mM) plus H2O2 (10nM), or iii) glucose (0, 5 or 10mM) plus phenolic acids (10-160nM). Fructosamine was measured using the nitroblue tetrazolium method.<p></p> Results: Following (high) dietary polyphenol intake, 3-hydroxyphenylacetic acid is the most abundant phenolic acid in peripheral blood (up to 338μM) with concentrations for other phenolic acids ranging from 13nM-200μM. Presence of six phenolic acids with BSA during in-vitro glycation did not lower fructosamine formation. However, when BSA was pre-incubated with phenolic acids, significantly lower concentration of fructosamine was detected under glycoxidative conditions (glucose 5 or 10mM plus H2O2 10nM) (p<0.001 vs. native BSA).<p></p> Conclusion: Protein pre-treatment, either with oxidants or phenolic acids, is an important regulator of subsequent glycation in a physiologically relevant system. High quality in-vitro studies under conditions closer to physiology are feasible and should be employed more frequently.<p></p&gt

Changing distributions of body size and adiposity with age

Background: Adiposity and health risks are better indicated by waist circumference than body mass index (BMI). Patterns of change with age are incompletely documented.<p></p> Methods: Adults aged 18–92 years in the Scottish and English Health Surveys of 1994–96 and 2008–10 were divided into fifteen 5-year age bands. Sex-specific prevalences of overweight/obesity and of increased/high waist circumference against age were compared using analysis of covariance. <p></p> Results: Data available for 7932 Scottish and 55 925 English subjects in 1994–96, and for 27 391 Scottish and 30 929 English in 2008–10, showed generally similar patterns of change in the two countries. Prevalences of both elevated BMI and waist circumference rose with age for longer in 2008–10 than in 1994–96, reaching higher peaks at greater ages, particularly among men. Between 1994–96 and 2008–10, maximum prevalences of BMI >30 increased from 25 to 38% (larger increases in men than women), reaching a peak at age 60–70 years in both sexes. This peak prevalence was 5–10 years later than in 1994–96 for men and remained unchanged for women. Between 1994–96 and 2008–10, maximum prevalences of high waist circumference (men>>102 cm, women>88 cm) increased from 30 to –70% in both sexes, peaking in 2008–10 at ages 80–85 years (men) and 65–70 years (women). In 2008–10, proportions of adults with ‘normal’ BMI (18.5–25) fell with age to 15–20% at age 60–70 years (men) and 75 years (women). Among all those with BMI=18.5–25, aged>65 years, the proportions with unhealthily elevated waist circumference were 30 (men>94 cm) and 55% (women>80 cm). <p></p> Conclusions: Almost 40% of men and women are now becoming obese. People are growing fatter later in life, with waist circumference rising more persistently than BMI, which may indicate increased loss of muscle mass and sarcopenia in old age. Among older people, few now have ‘normal’ BMI, and of these up to half have elevated waist circumference, raising questions for the suitability of BMI as a measure of adiposity in this age group. <p></p&gt

Tailoring the flow of soft glasses by soft additives

We examine the vitrification and melting of asymmetric star polymers mixtures by combining rheological measurements with mode coupling theory. We identify two types of glassy states, a {\it single} glass, in which the small component is fluid in the glassy matrix of the big one and a {\it double} glass, in which both components are vitrified. Addition of small star polymers leads to melting of {\it both} glasses and the melting curve has a non-monotonic dependence on the star-star size ratio. The phenomenon opens new ways for externally steering the rheological behavior of soft matter systems.Comment: 4 pages, 4 figures, accepted in Phys. Rev. Let

Role of oxidative stress in physiological albumin glycation: a neglected interaction

Protein glycation is a key mechanism involved in chronic disease development in both diabetic and nondiabetic individuals. About 12–18% of circulating proteins are glycated in vivo in normoglycemic blood, but in vitro studies have hitherto failed to demonstrate glucose-driven glycation below a concentration of 30 mM. Bovine serum albumin (BSA), reduced BSA (mercaptalbumin) (both 40 g/L), and human plasma were incubated with glucose concentrations of 0–30 mM for 4 weeks at 37 °C. All were tested preoxidized for 8 h before glycation with 10 nM H2O2 or continuously exposed to 10 nM H2O2 throughout the incubation period. Fructosamine was measured (nitroblue tetrazolium method) at 2 and 4 weeks. Oxidized BSA (both preoxidized and continuously exposed to H2O2) was more readily glycated than native BSA at all glucose concentrations (p = 0.03). Moreover, only oxidized BSA was glycated at physiological glucose concentration (5 mM) compared to glucose-free control (glycation increased by 35% compared to native albumin, p < 0.05). Both 5 and 10 mM glucose led to higher glycation when mercaptalbumin was oxidized than when unoxidized (p < 0.05). Fructosamine concentration in human plasma was also significantly higher when oxidized and exposed to 5 mM glucose, compared to unoxidized plasma (p = 0.03). The interaction between glucose concentration and oxidation was significant in all protein models (p < 0.05). This study has for the first time demonstrated albumin glycation in vitro, using physiological concentrations of albumin, glucose, and hydrogen peroxide, identifying low-grade oxidative stress as a key element early in the glycation process

Multi-Particle Collision Dynamics -- a Particle-Based Mesoscale Simulation Approach to the Hydrodynamics of Complex Fluids

In this review, we describe and analyze a mesoscale simulation method for fluid flow, which was introduced by Malevanets and Kapral in 1999, and is now called multi-particle collision dynamics (MPC) or stochastic rotation dynamics (SRD). The method consists of alternating streaming and collision steps in an ensemble of point particles. The multi-particle collisions are performed by grouping particles in collision cells, and mass, momentum, and energy are locally conserved. This simulation technique captures both full hydrodynamic interactions and thermal fluctuations. The first part of the review begins with a description of several widely used MPC algorithms and then discusses important features of the original SRD algorithm and frequently used variations. Two complementary approaches for deriving the hydrodynamic equations and evaluating the transport coefficients are reviewed. It is then shown how MPC algorithms can be generalized to model non-ideal fluids, and binary mixtures with a consolute point. The importance of angular-momentum conservation for systems like phase-separated liquids with different viscosities is discussed. The second part of the review describes a number of recent applications of MPC algorithms to study colloid and polymer dynamics, the behavior of vesicles and cells in hydrodynamic flows, and the dynamics of viscoelastic fluids

Reactive Transport Modeling of Subaqueous Sediment Caps and Implications for the Long-Term Fate of Arsenic, Mercury, and Methylmercury

A 1-D biogeochemical reactive transport model with a full set of equilibrium and kinetic biogeochemical reactions was developed to simulate the fate and transport of arsenic and mercury in subaqueous sediment caps. Model simulations (50 years) were performed for freshwater and estuarine scenarios with an anaerobic porewater and either a diffusion-only or a diffusion plus 0.1-m/year upward advective flux through the cap. A biological habitat layer in the top 0.15 m of the cap was simulated with the addition of organic carbon. For arsenic, the generation of sulfate-reducing conditions limits the formation of iron oxide phases available for adsorption. As a result, subaqueous sediment caps may be relatively ineffective for mitigating contaminant arsenic migration when influent concentrations are high and sorption capacity is insufficient. For mercury, sulfate reduction promotes the precipitation of metacinnabar (HgS) below the habitat layer, and associated fluxes across the sediment–water interface are low. As such, cap thickness is a key design parameter that can be adjusted to control the depth below the sediment–water interface at which mercury sulfide precipitates. The highest dissolved methylmercury concentrations occur in the habitat layer in estuarine environments under conditions of advecting porewater, but the highest sediment concentrations are predicted to occur in freshwater environments due to sorption on sediment organic matter. Site-specific reactive transport simulations are a powerful tool for identifying the major controls on sediment- and porewater-contaminant arsenic and mercury concentrations that result from coupling between physical conditions and biologically mediated chemical reactions

The influence of sulfur and iron on dissolved arsenic concentrations in the shallow subsurface under changing redox conditions

The chemical speciation of arsenic in sediments and porewaters of aquifers is the critical factor that determines whether dissolved arsenic accumulates to potentially toxic levels. Sequestration of arsenic in solid phases, which may occur by adsorption or precipitation processes, controls dissolved concentrations. We present synchrotron x-ray absorption spectra of arsenic in shallow aquifer sediments that indicate the local structure of realgar (AsS) as the primary arsenic-bearing phase in sulfate-reducing conditions at concentrations of 1-3 mmol(.)kg(-1), which has not previously been verified in sediments at low temperature. Spectroscopic evidence shows that arsenic does not substitute for iron or sulfur in iron sulfide minerals at the molecular scale. A general geochemical model derived from our field and spectroscopic observations show that the ratio of reactive iron to sulfur in the system controls the distribution of solid phases capable of removing arsenic from solution when conditions change from oxidized to reduced, the rate of which is influenced by microbial processes. Because of the difference in solubility of iron versus arsenic sulfides, precipitation of iron sulfide may remove sulfide from solution but not arsenic if precipitation rates are fast. The lack of incorporation of arsenic into iron sulfides may result in the accumulation of dissolved As(III) if adsorption is weak or inhibited. Aquifers particularly at risk for such geochemical conditions are those in which oxidized and reduced waters mix, and where the amount of sulfate available for microbial reduction is limited