Keratin hydration

In 1994 Forslind presented a more structure-function orientated model, the domain mosaic model.38 With the background given previously, the requirements on the stratum corneum barrier can be summarized as follows the barrier should be watertight but still allow a small, controlled amount of water to leak from the system in order to keep the corneocyte keratin hydrated. 

Penetration of dimethyl phosphite into the fibre, accompanied by decomposition of salt linkages and elimination of structural water in a multi-step hydration process. New salt linkages are formed between cationic groups in wool keratin and anionic dimethyl phosphite. 

Room temperature phosphorescence can be observed from dried proteins. Sheep wool keratin(47) has a phosphorescence lifetime of 1.4 s. Six lyophilized proteins were shown to exhibit phosphorescence at room temperature.(48) The spectra were diffuse, and the lifetime was non-single-exponential, which the authors interpreted as due to inhomogeneous distribution of tryptophans. As the protein was hydrated, the phosphorescence lifetime decreased. This decrease occurred over the same range of hydration where the tryptophan fluorescence becomes depolarized. Hence, these results are consistent with the idea that rigidity of the site contributes to the lifetimes. 

The skin barrier properties and effect of hand hygiene practices are known to be important in protecting the body. The average adult has a skin area of about 1.75 m2. The superficial part of the skin, the epidermis, has five layers. The stratum corneum, the outermost layer, is composed of flattened dead cells (comeocytes or squames) attached to each other to form a tough, homy layer of keratin mixed with several lipids, which help maintain the hydration, pliability, and barrier effectiveness of the skin. This part of skin has been compared to a wall of bricks (comeocytes) and mortar (lipids) and serves as the primary protective barrier. Approximately 15 layers make up the stratum corneum, which is completely replaced every 2 weeks a new layer is formed almost daily. From healthy skin, approximately 107 particles are disseminated into the air each day, and 10% of these skin squames contain viable bacteria. This is a source of major dirt inside the house and contributes to many interactions. 

Uses Mild cervicitis, postpartum cervicitis/cervical tears, post cauterization, post cryosurgery, post conization Action Hydrating agent removes excess keratin in hyperkeratotic conditions Dose 1 applicator full intravag hs x 2- wk Caution [C, ] w/ viral skin Infxn Disp Vag cream SE Stinging, local irritation EMS None OD Unlikely to produce life-threatening Sxs... 

Bonding Forces Between Dye and Fiber. Dye anions can participate in ionic interactions with fibers that possess cationic groups. However, the formation of ionic bonds is not sufficient to explain dye binding, because compounds that can dissociate are cleaved in the presence of water. Secondary bonds (dispersion, polar bonds, and hydrogen bonds) are additionally formed between dye and fiber [47], Close proximity between the two is a prerequisite for bond formation. However, this is counteracted by the hydration spheres of the dye and of wool keratin. On approach, these spheres are disturbed, especially at higher temperature, and common hydration spheres are formed. The entropy of the water molecules involved is increased in this process (hydrophobic bonding). In addition, coordinate and covalent bonds can be superimposed on secondary and ionic bonds. 

Water homeostasis is a strict requirement for normal physiological function. The most important task of the human skin is thus to create a watertight enclosure of the body to prevent water loss. It is the intercellular lipid matrix of the outermost keratinized horny layer of the skin (possibly together with recently reported claudin-based tight-junctions Furuse et al., 2002) that represents the skin barrier proper as once this lipid matrix (composed foremostly of saturated long chain ceramides ( 50% wt/wt) and cholesterol (—30% wt/wt) (Wertz and Norlen, 2002)) has been removed, substances diffuse freely into or out of the body system (Blank, 1952 Breathnach et al., 1973 Elias and Friend, 1975). At the same time the intercellular lipid matrix ensures that the stratum corneum remains hydrated and thus the skin surface appears healthy and smooth. 

Most recently, Nakagawya et al.34 demonstrated that topical application of potassium lactate restored stratum corneum hydration after NMF extraction and exhibited a significantly higher restorative effect than sodium lactate. The authors speculate that this is due to the structure-destructive properties of the potassium ion and may influence hydrogen bonding in the keratin matrix. 

Wilkes et al (22.23) coupled calorimetric, dynamic-mechanical and x-ray diffraction techniques to demonstrate crystallization of the lipids was completely reversible in neonatal rat stratum corneum, and only partially reversible in human stratum corneum. Melting regions near 40°C and from 70 to 90°C corresponded to the thermal transitions noted in the calorimetric studies for both species. The crystalline nature of the lipids did not appear to be dependent on the presence of water. X-ray diffraction and infrared spectroscopy studies (23.28-34) have also shown a to p conformational changes occurred in keratin and stratum corneum protein components with hydration or exposure to increased temperatures. Oertel (28) has reported pretreatment with dimethylsulfox-ide, hexylmethylsulfoxide and decylmethylsulfoxide resulted in the formation of p-sheet protein conformations in vitro in human... 

Depolarization thermal studies have been reported by Leveque et al. (1981) for partially hydrated keratin, by Bridelli et al. (1985) for lysozyme, and by Anagnostopoulou-Konsta and Pissis (1987) for casein. These studies reveal a rich and complex thermal depolarization spectrum, shown in Fig. 16. It is difficult to explain the spectrum with a model based on the reorientation of noninteracting dipoles with a few distinct relaxation times. Pissis and colleagues (personal communication... 

While a temperature-dependent IR spectrum allows one to examine specific elements of a transition, a DSC thermogram enables the visualization of transitions in their entirety and the calculation of associated thermodynamic parameters. The IR and DSC thermal profiles for identically treated samples of hydrated porcine SC are shown in Fig. 3. The results of a series of thermograms for intact, delipidized, fractionated, and reheated SC as well as extracted lipids suggest that these three major transitions near 60,70, and 95°C in intact SC are due to intercellular lipid, a lipid-protein complex associated with the comeocyte membrane, and intracellular keratin, respectively. Evidence supporting these deductions is elegantly presented by Golden et al. [33]. More recently, the presence of a subzero lipid transition at -9°C has also been reported [34]. 

The complexity of the SC membrane hinders such definitive interpretation, but, nevertheless, alterations in endotherms can be used to screen molecules suspected of altering membrane function. Conversely, one should note that the absence of additive-induced alterations in the phase transition profile does not rale out their perturbing effect, but rather indicates that the additive does not modify the gel phase. As described earlier, a DSC thermogram of hydrated but untreated human SC yields four endotherms, the first three of which can be identified as noncooperative lipid-associated phase transitions, while the high-temperature endotheim is attributed to keratin denaturation [33,37]. 

Since hydration of the skin has been shown to be the primary variable influencing the skin s impedance [7,10,11,18], one can speculate that the time variation in the skin s impedance may be a strong function of the time variation of the skin s hydration. The reason for the skin s profound dependence on hydration results from the skin s hydroscopic nature [15] coupled with water s significant impact on the skin s dielectric constant [12]. The skin s hydroscopic characteristic is speculated to be in part due to the presence of amino acids in the skin [15]. Hydration probably influences the skin s dielectric constant because the following components are sensitive to an electric field [7] (a) The keratin protein chains contained in the stratum comeum have a dipole moment. Thus, as the stratum comeum becomes more hydrated, the keratin becomes more flexible and responsive to an applied electric field, (b) As the stratum comeum becomes more hydrated, the ions in the stratum comeum become freer to move and thus more responsive to an applied electric field. 

The wide angle x-ray diffraction pattern of undeformed corneum exhibits diffuse halos at 4.6 A and 9.8 A common to proteins (Figure 4). The lack of the 5.1-A reflection characteristic of alpha-keratin structures in undeformed comeum suggests that the protein is considerably less oriented and perhaps of a lower alpha content than wool. This is supported by the fact that the 5.1-A reflection begins to appear in samples of comeum which were hydrated and stretched to 100% or more (Figure 6) and allowed to dry in the extended state. The increased orientation of the lipid reflections in the stretched sample demonstrates further their association with the orienting protein fibrils. 

X-ray diffraction and IR dichroism studies suggest that the long-range elasticity of wool is related to a reversible molecular transformation of the alpha-keratin to an extended beta form (66). No convincing evidence supports this mechanism in stratum corneum viscoelasticity. In fact, the available evidence suggests that the elastic behavior of corneum is primarily entropic in origin. At low deformations, the mechanical properties of hydrated stratum corneum is best described as the behavior of a lightly-crosslinked rubber. 

The external auditory canal skin is normally acidic, with a pH level between 4 and 5. Keratin, which consists of desquamated epithelial cells, is produced by the epithelial (skin) lining of the external ear canal it has an isoelectric point of pH 5. Any increase above this value causes hydration of the keratin layer, increasing susceptibility to pathogenic organisms. Because as most organisms responsible for otitis... 

The stratum corneum is the outermost layer of the epidermis and has a thickness of 10-15 pm. It is the principal barrier for the transport of most solutes (except for very lipophilic compounds) across the skin. The stratum corneum is a continuous heterogeneous structure that consists of approximately 10-25 layers of closely packed dead keratinized cells (corneocytes) cemented together by intercellular lipids. The intercellular lipids in the stratum corneum are in the form of multiple lamellar bilayers composed mainly of ceramides, cholesterol, and fatty acids. Proteins in the stratum corneum are largely concentrated within the corneocytes as keratin fibrils. The transport of lipophilic compounds across the stratum corneum is related to the intercellular lipids (lipoidal or intercellular pathways). On the other hand, it is believed that the transport of polar and ionic compounds is related to pathways with aqueous properties (the polar or pore pathways) when the stratum corneum is under a hydrated state. ... 

The physicochemical factors that control dmg penetration include the hydration of the stratum corneum, temperature, pFT, drug concentration, and the molecular characteristics of the penetrant and the vehicle. The stratum corneum is a heterogeneous stmcture containing about 40% protein (keratin, a disul-fide-crosslinked linear polypeptide), about... 

Many modern dermatological formulations are washable oil-in-water systems. Simple aqueous lotions are also used as they have a cooling effect on the skin. Ointments are used for the application of insoluble or oil-soluble medicaments and leave a greasy film on the skin, inhibiting loss of moisture and encouraging the hydration of the keratin layer. Aqueous creams combine the characteristics of the lotions and ointments. A classification of semisolid bases is given in Fig. 9.24. 

Application site Epidermal and stratum corneum thickness, keratinization, blood flow, hair follicles/glands, skin condition (dermatoses, damage, hydration state, occlusion, pH)... 

At concentrations above 2% salicylic acid has a keratolytic effect, causing the keratin layer of the skin to shed. Keratolysis is achieved by increasing the hydration of the stratum corneum, softening the cells and facilitating dissolution of the intracellular cement that bonds the cells together so that they separate and detach (desquamate). Moisture is essential to this process and is provided by either the water in the formulation or the occlusive effect produced by its application to the skin. 

Oromucosal 0.02 m easily accessible Mucus, stratified, partly keratinized epithelium (500-600 pm), hydrated -h-h-h 0-5%... 

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