Vitamin c—sources, physiological role, kinetics, deficiency, use, toxicity, and determination

Vitamin C (L‐ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facili-tation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro‐oxidant than an anti‐oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence—scurvy. The only clini-cally well‐documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is relatively safe, but caution should be given to the administration of high doses, which can cause overt side effects in some susceptible patients (e.g., oxalate renal stones). Lastly, analytical methods for its determination with advantages and pitfalls are also discussed in this review

Influence of ionic strength changes on the structure of pre-adsorbed salivary films. A response of a natural multi-component layer

Salivary films coating oral surfaces are critically important for oral health. This study focuses on determining the underlying nature of this adsorbed film and how it responds to departures from physiological conditions due to changes in ionic strength. Under physiological conditions, it is found that pre-adsorbed in vitro salivary film on hydrophobic surfaces is present as a highly hydrated viscoelastic layer. We follow the evolution of this film in terms of its effective thickness, hydration and viscoelastic properties, as well as adsorbed mass of proteins, using complementary surface characterisation methods: a Surface Plasmon Resonance (SPR) and a Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D). Our results support a heterogeneous model for the structure of the salivary film with an inner dense anchoring layer and an outer highly extended hydrated layer. Further swelling of the film was observed upon decreasing the salt concentration down to 1 mM NaCl. However, upon exposure to deionised water, a collapse of the film occurs that was associated with the loss of water contained within the adsorbed layer. We suggest that the collapse in deionised water is driven by an onset of electrostatic attraction between different parts of the multi-component salivary film. It is anticipated that such changes could also occur when the oral cavity is exposed to food, beverage, oral care and pharmaceutical formulations where drastic changes to the structural integrity of the film is likely to have implications on oral health, sensory perception and product performance. © 2010 Elsevier B.V. All rights reserved

Influence of ionic strength on the tribological properties of pre-adsorbed salivary films

We have studied tribological properties of pre-adsorbed salivary films formed in vitro on compliant hydrophobic surfaces. The adsorbed salivary film significantly decreases boundary friction under physiological ionic strength, which is related to a hydrophilic character of the adsorbed film and its structure. Decrease in the ionic strength below physiological conditions affects film's structure, but it does not significantly affect boundary lubrication at low loads. Applications of high loads led to a gradual loss of lubrication due to shear-induced wear of the films. The wear became more extensive as the ionic strength of the solvent was lowered below physiological conditions. (C) 2011 Published by Elsevier Ltd

Aqueous lubrication by fractionated salivary proteins: synergistic interaction of mucin polymer brush with low molecular weight macromolecules

The remarkable lubrication provided by saliva in the oral cavity is vital to human health and wellbeing. Yet, molecular mechanisms for saliva lubrication remain unclear. In this work we report a possible mechanism of synergistic interaction between salivary proteins. By isolating a number of salivary protein fractions, we identify major protein candidates that contribute to saliva lubrication. We discover that a key driver for low friction is a hydrated brush-like layer formed by glycosylated species, with an essential synergistic contribution coming from the low molecular weight components that facilitate spreading, adsorption and strengthening of the salivary film on hydrophobic substrates. Lessons may be learned from saliva for understanding other natural bio-aqueous lubrication systems and for the development of saliva mimics

A transgenic minipig models of Huntington’s disease

Background: Some promising treatments for Huntington\u2019s disease (HD) may require pre-clinical testing in large animals. Minipig is a suitable species because of its large gyrencephalic brain and long lifespan. Objective: To generate HD transgenic (TgHD) minipigs encoding huntingtin (HTT)1\u2013548 under the control of human HTT promoter. Methods: Transgenesis was achieved by lentiviral infection of porcine embryos. PCR assessment of gene transfer, observations of behavior, and postmortem biochemical and immunohistochemical studies were conducted. Results: One copy of the human HTT transgene encoding 124 glutamines integrated into chromosome 1 q24-q25 and successful germ line transmission occurred through successive generations (F0, F1, F2 and F3 generations). No developmental or gross motor deficits were noted up to 40 months of age. Mutant HTTmRNAand protein fragment were detected in brain and peripheral tissues. No aggregate formation in brain up to 16 months was seen by AGERA and filter retardation or by immunostaining. DARPP32 labeling in WT and TgHD minipig neostriatum was patchy. Analysis of 16 month old siblings showed reduced intensity of DARPP32 immunoreactivity in neostriatal TgHD neurons compared to those of WT. Compared to WT, TgHD boars by one year had reduced fertility and fewer spermatozoa per ejaculate. In vitro analysis revealed a significant decline in the number of WT minipig oocytes penetrated by TgHD spermatozoa. Conclusions: The findings demonstrate successful establishment of a transgenic model of HD in minipig that should be valuable for testing long term safety of HD therapeutics. The emergence of HD-like phenotypes in the TgHD minipigs will require more study