Barrier function of skin

Soap as used in personal cleansing products has a long safe history of use. Modem soaps have been specifically formulated to be compatible with skin and to be used on a daily basis with minimal side effects. Excessive use of soap for skin cleansing can dismpt the natural barrier function of skin through the removal of skin oils and dismption of the Hpid bdayer in skin. This can result in imperfect desquamation or a dry appearance to skin and cause an irritation response or erythema, ie, reddening of the skin. Neither of these is a permanent response and the eHcitation of this type of skin reaction depends on the individual s skin type, the product formulation, and the frequency of use. 

Diffusion of aqueous material through the epidermis is blocked by these lipids synthesized by keratinocytes in the stratum granulosum, the boundary corresponding to the level at which HA-staining ends. This constitutes part of the barrier function of skin. The HA-rich area inferior to this layer may obtain water from the moisture-rich dermis. And the water contained therein cannot penetrate... 

The barrier function of skin is attributed predominantly to its outermost layer, the stratum corneum, which protects the body from a percutaneous penetration of compounds and from desiccation, thus permitting terrestrial mammals to control their internal aqueous balance and to survive in a nonaqueous environment. Stratum corneum lipids have highly specific composition and organization and play an important role in the skin... 

Roberts, M.S. Walters, K.A. The relationship between structure and barrier function of skin. In Dermal Absorption and Toxicity Assessment, Roberts, M.S., Walters, K.A., Eds. Marcel Dekker New York, 1998. 

Hadgraft, J. (2001). Modulation of the barrier function of skin. Skin Pharmacol. Appl. Skin Physiol, 14(suppl 1) 72-81. 

Fatty acids play an important role in the barrier function of skin and represent a major source of proinflammatory mediators such as prostaglandins, leukotrienes and other lipids in inflammatory skin disorders. This book combines the two major functions of fatty acids in skin biology. 

One of the available method to improve the transdermal absorption of drugs is to reduce this barrier function of skin by the aid of enhancers. 

The amounts of ointments and creams people apply are highly individualized. So are the techniques of application. Some patients vigorously rub semisolid formulations into the skin, while others just spread films until they are more or less uniform over the desired area. While pharmacokinetic assessments of a system s delivery attributes is ordinarily done using normal skin (in vitro) or on healthy volunteers (in vivo), the site of its clinical deployment is usually anything but normal. Rather, it is determined by the skin condition to be treated. Clearly, the manufacturer is without control over how a disease is expressed in a particular patient. For many diseases, disease manifestation can be anywhere on the body. Moreover, from individual to individual it varies in intensity and vastness. Thus, more area may be involved in one case than in another, and the barrier function of the skin may be more or less intact in any instance. This creates a set of imponderables with respect to delivery, efficacy, and safety. 

The stratum corneum consists of separated, nonviable, cornified, almost nonpermeable corneocytes embedded into a continuous lipid bilayer made of various classes of lipids, for example, ceramides, cholesterol, cholesterol esters, free fatty acids, and triglycerides [6], Structurally, this epidermis layer is best described by the so-called brick-and-mortar model [7], The stratum corneum is crucial for the barrier function of the skin, controlling percutaneous absorption of dermally applied substances and regulating fluid homeostasis. The thickness of the stratum corneum is usually 10-25 /an, with exceptions at the soles of the feet and the palms, and swells several-fold when hydrated. All components of the stratum corneum originate from the basal layer of the epidermis, the stratum germinativum. 

The human skin model assay involves measuring the effects of corrosives on viable cells in a reconstituted human skin equivalent. To be accepted as a valid human skin model, several criteria must be met. The artificial skin must comprise a functional stratum corneum with an underlying layer of viable cells. Furthermore, the barrier function of the stratum corneum, as well as the viability of the epidermis, must be verified with appropriate experimental setups. The chemicals to be tested are applied up to 4 h as a liquid or a wet powder onto the skin model. Afterwards, careful washing has to be performed, followed by investigation of the cell viability [e.g., with a (MTT)] reduction assay). 

A. Schatzlein and G. Cevc. Non-uniform cellular packing of the stratum corneum and permeability barrier function of intact skin a high-resolution confocal laser scanning microscopy study using highly deformable vesicles (Transfersomes). Br. J. Dermatol. 138 583-592 (1998). 

Wertz, P.W., Lipids and barrier function of the skin, Acta Derm. Venerol., 208, 1,2000. 

These findings suggested that the decrease in free amino acids (= NMF) and inferior barrier function of SC caused the dry skin of AD patients, but the decrease of NMF mainly caused the dry skin in HD patients. 

The TEWL in both regions was three to four times higher in AD patients than in the control (Figure 9.2), and the lesional skin gave higher values than the nonlesional skin (p < 0.05). On the other hand, the TEWL was only slightly higher in HD patients than in the control (mean value HD patients, 7.0 g/m2/h, the control, 5.0 g/m2/h). The barrier function of SC in HD patients was similar to that in the control. 

The characteristics of hydration level and barrier function of SC in various types of dry skin were reviewed and summarized in Table 9.3. They are senile xerosis, seasonal allergic rhinitis, ichthyosis valgaris, and experimentally induced dry skin including atopic xerosis and dry skin by hemodialysis. The water content decreased in every type of dry skin and the free amino acids content also decreased corresponding to the decrease of the water content. However, the TEWL or the ceramide levels showed no clear tendency throughout every type of dry skin, especially ceramides showed higher or lower value even though the water content in SC was consistently lower in every type of dry skin. 

The water content in SC was low both in AD and HD patients, and their skin was obviously dry. However, there was a great difference between them in TEWL. The TEWL was high in AD patients accompanied with extremely inferior barrier function of SC, while HD patients showed a slightly higher TEWL than the controls and their barrier function proved to be in the mostly normal range. The findings obtained in HD patients resembled the symptoms of senile xerosis20,21 and coincided with those reported by Kamiya et al.11 The difference in TEWL between AD and HD patients and the... 

AD patients showed mild inflammation with induction of the parakeratosis, decreased moisture holding ability, and inferior barrier function, while HD patients showed only reduced moisture holding ability with almost normal skin barrier function but without inflammation. Then, it was concluded that the dry skin of AD patients resulted from the lack of moisture holding factor (free amino acids, NMF) and inferior barrier function of SC, while that in HD patients was mainly attributed to the decrease of the moisture holding factors. 

Dry, scaly skin is characterized by a decrease in the water retention capacity of the stratum corneum (SC),1 with water content diminished to less than 10%. Barrier function of the SC is usually declined, and transepidermal water loss (TEWL) is increased because of an abnormality on barrier homeostasis.2 People feel tightness of their skin, and the skin surface becomes rough, scaly, and sensitive. Hyperkeratosis, abnormal scaling, and epidermal hyperplasia are usually observed in the dry skin.2 Keratinization also shows abnormal features.2 These phenomena are commonly observed in atopic dermatitis and psoriasis.3 Dermatitis induced by environmental factors such as exposure to chemicals, low humidity, and UV radiation also shows these features. Thus, many researchers have been investigating the cause and treatment of dry skin, and there is currently great interest in adequate model systems for dry skin studies. In this chapter, I will describe several model systems of dry skin for clinical research of dermatitis associated with skin surface dryness and also mention recent studies to improve the dry skin. 

The considerations mentioned earlier also bring up the subsequent questions that wait to be answered, for example, about the influence of moisturizers on pH-gradient inside the epidermis and the activity of enzymes, effect on skin barrier function and skin barrier recovery, or the difference in... 

Thune, P. et al., The water barrier function of the skin in relation to the water content of stratum corneum, pH and skin lipids. The effect of alkaline soap and syndet on dry skin in elderly, non-atopic patients, Acta Derm. Venereol., 68, 277, 1988. 

HP3 is of questionable physiological significance. As expected, in both in vitro and in vivo models, a strong occlusion was seen after application of white petrolatum. This strong occlusive effect as observed with the lipophilic pastes led to a diminution of the TEWL because of the concomitant increase in the barrier function of the stratum corneum and despite an accumulation of moisture in the horny layer. This justifies the use of such pastes for skin protection, but not for drying the skin. 

Consumers use moisturizers frequently, especially women use them often on twice daily basis for years or even decades. Therefore it is appropriate to ask for the consequences of this life-long treatment on the barrier function of the skin. Fortunately we do not see adverse reactions after... 

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