Molecular Mobility in Keratin-Rich Materials Monitored by Nuclear Magnetic Resonance: A Tool for the Evaluation of Structure-Giving Properties.

Keratins are structural proteins that are abundant in human skin, nails, and hair, where they provide mechanical strength. In the present study, we investigate the molecular mobilities and structures of three keratin-rich materials with clearly different mechanical properties: nails, stratum corneum (upper layer of epidermis), and keratinocytes (from lower layer of epidermis). We use solid-state NMR on natural-abundance 13C to characterize small changes in molecular dynamics in these biological materials with close to atomistic resolution. One strong advantage of this method is that it detects small fractions of mobile components in a molecularly complex material while it simultaneously gives information on the rigid components in the very same sample. The molecular mobility can be linked to mechanical material properties in different conditions, including hydration or exposure to osmolytes or organic solvents. Importantly, the study revealed that the response to both hydration and addition of urea is clearly different for the nail keratin compared to the stratum corneum keratin. The comparative examination of these materials may provide a better understanding of skin diseases originating from keratin malfunction and contributes to the design and development of new materials.

The effects of glycols on molecular mobility, structure, and permeability in stratum corneum.

The skin provides an attractive alternative to the conventional drug administration routes. Still, it comes with challenges as the upper layer of the skin, the stratum corneum (SC), provides an efficient barrier against permeation of most compounds. One way to overcome the skin barrier is to apply chemical permeation enhancers, which can modify the SC structure. In this paper, we investigated the molecular effect of three different types of glycols in SC: dipropylene glycol (diPG), propylene glycol (PG), and butylene glycol (BG). The aim is to understand how these molecules influence the molecular mobility and structure of the SC components, and to relate the molecular effects to the efficiency of these molecules as permeation enhancers. We used complementary experimental techniques, including natural abundance 13C NMR spectroscopy and wide-angle X-ray diffraction to characterize the molecular consequences of these compounds at different doses in SC at 97% RH humidity and 32 °C. In addition, we study the permeation enhancing effects of the same glycols in comparable conditions using Raman spectroscopy. Based on the results from NMR, we conclude that all three glycols cause increased mobility in SC lipids, and that the addition of glycols has an effect on the keratin filaments in similar manner as Natural Moisturizing Factor (NMF). The highest mobility of both lipids and amino acids can be reached with BG, which is followed by PG. It is also shown that one reaches an apparent saturation level for all three chemicals in SC, after which increased addition of the compound does not lead to further increase in the mobility of SC lipids or protein components. The examination with Raman mapping show that BG and PG give a significant permeation enhancement as compared to SC without any added glycol at corresponding conditions. Finally, we observe a non-monotonic response in permeation enhancement with respect to the concentration of glycols, where the highest concentration does not give the highest permeation. This is explained by the dehydration effects at highest glycol concentrations. In summary, we find a good correlation between the molecular effects of glycols on the SC lipid and protein mobility, and macroscopic permeation enhances of the same molecules.

Extraction of natural moisturizing factor from the stratum corneum and its implication on skin molecular mobility.

The natural moisturizing factor (NMF) is a mixture of small water-soluble compounds present in the upper layer of the skin, stratum corneum (SC). Soaking of SC in water leads to extraction of the NMF molecules, which may influence the SC molecular properties and lead to brittle and dry skin. In this study, we investigate how the molecular dynamics in SC lipid and protein components are affected by the removal of the NMF compounds. We then explore whether the changes in SC components caused by NMF removal can be reversed by a subsequent addition of one single NMF component: urea, pyrrolidone carboxylic acid (PCA) or potassium lactate. Samples of intact SC were investigated using NMR, X-ray diffraction, infrared spectroscopy and sorption microbalance. It is shown that the removal of NMF leads to reduced molecular mobility in keratin filaments and SC lipids compared to untreated SC. When the complex NMF mixture is replaced by one single NMF component, the molecular mobility in both keratin filaments and lipids is regained. From this we propose a general relation between the molecular mobility in SC and the amount of polar solutes which does not appear specific to the precise chemical identify of the NMF compounds.

On the interference of urea with CO2/CO32- chemistry of cellulose model solutions in NaOH(aq).

The CO2/CO32- chemistry of the cellulose/NaOH(aq) solutions has been recently reported to comprise a CO2 incorporation through formation of a transient cellulose carbonate intermediate along with cellulose - CO32- interactions. This work explores on molecular interactions arising when this chemistry is brought together with urea, the most common stabiliser of these solutions. 1H, 13C and steady-state heteronuclear Overhauser effect NMR studies on the cellulose analogues (methyl-ß-glucopyranoside (ß-MeO-Glcp) and microcrystalline cellulose), combined with pH and ATR-FTIR measurements, reveal concurrent interactions of urea with both CO2 and CO32-- leading to increased uptake of CO2 and a buffering effect. Yet, regardless of the presence of urea, the route of conversion from CO2 to CO32-, whether going through reaction with the carbohydrate alkoxides or OH-, is likely to determine the chemical environment of the formed CO32-. These findings shed a new light on rather overlooked, albeit prominent, interactions in these solutions with the readily absorbed air CO2, essential for further development and implementation, whether towards regenerated and modified cellulose or CO2-capturing concepts.

In primary health care, never prescribe antibiotics to patients suspected of having an uncomplicated sore throat caused by group A beta-haemolytic streptococci without first confirming the presence of this bacterium.

BACKGROUND: There are several consensus-describing decision rules for patients in primary health care with a sore throat. The objective of this study was to estimate the number of unnecessary antibiotic prescriptions in primary health care given to patients with a sore throat, due to these different decision rules. A further aim was to suggest revised rules for decision-making in primary health care, when a sore throat caused by group A beta-haemolytic streptococci (GAS) is suspected. METHODS: The design was a reanalysis of previously published articles describing the prevalence of GAS and physician behaviour when treating patients with a sore throat. The risk of unnecessary antibiotic prescribing in different situations was estimated and applied to the Swedish population. RESULTS: Introducing the rule of never prescribing antibiotics without first confirming the presence of GAS would result in an annual reduction in Sweden of 20,360-25,192 unnecessary antibiotic prescriptions in children and 65,311-98,160 in adults. CONCLUSIONS: The single most important rule in primary health care to minimize the risk of unnecessary antibiotic prescription to patients with an uncomplicated sore throat, and where an infection with GAS is suspected, is to never prescribe antibiotics at the first visit without first confirming the presence of this bacterium. Adding more decision rules may to some extent further reduce the number of unnecessary antibiotic prescriptions.