Skin and Epithelial System

Toxic agents affecting the skin and epithelial systems, in particular the eyes, may either act directly through corrosive actions, as in the case of acids or alkalis, or cause damage through actions on DNA and protein synthesis. 

The skin and epithelial membranes are very susceptible to toxic trauma from a number of chemical agents. These range from the familiar corrosive actions of acids and alkalis to the vesication produced by mustard gas (HD) and similar CW agents. Some toxins also cause damage to the skin and epithelial system. Examples include mycotoxins and ricin, both of which have been considered to be CW agents. 

Mechanism of Action Modulates differentiation and proliferation of epithelial tissue, binds selectively to retinoic acid receptors. TherapeutkEffect Restores normal differentiation of the epidermis and promotes reduction of epidermal inflammation. Pharmacokinetics Minimal systemic absorption occurs through the skin. Binding to plasma proteins is greater than 99%. Metabolism is in the skin and liver. Elimination occurs through the fecal and renal pathways. Half-life 18 hr. 

Other Organs or Tissues of Potential Metabolic Importance The situation becomes much more complicated when tissues at the body s portals of entry are the focus of drug metabolism studies. Portals of entry include epithelial and other cells in various parts of the gut, cell layers of the skin, and cell linings in different parts of the bronchio-alveolar (pulmonary) system. Problems with these tissues and organs are multifaceted there are usually multiple... 

The purpose of this chapter is to present overviews of a selection of the major endothelial and epithelial barriers to drug delivery for which there are either primary culture or cell line systems that recapitulate the characteristics of the in vivo barrier. Our objective is to define some general characteristics of cell culture models and highlight the more commonly applied primary cell cultures and cell lines in use today. Specifically, we focus on cell culture models for the intestinal epithelium, blood-brain barrier, pulmonary and nasal epithelium, ocular epithelium, placental barrier, and renal epithelium. Renal epithelium was included here primarily because some cell lines derived from this tissue [e.g., Madin-Darby canine kidney cells (MDCK)] are often used as surrogates for other barriers by pharmaceutical scientists. We have arbitrarily chosen to exclude the skin and liver from the scope of this overview. However, it should be noted that hepatocyte cell culture models, for example, are becoming more widely available and have been the subject of recent reviews.1,2... 

A complex interplay of host and pathogen factors influences the acquisition and development of fungal infections. Intact skin or mucosal surfaces serve as primary barriers to infection. Desiccation, epithelial cell turnover, fatty acid content, and low pH of the skin are believed to be important factors in host resistance. Bacterial flora of the skin and mucous membranes compete with fungi for growth. Alterations in the balance of normal flora caused by the use of antibiotics or alterations in nutritional status can allow the proliferation of fungi such as Candida, increasing the likelihood of systemic invasion and infection. ... 

Defects in the structures of laminin 5 or laminin 6 (proteins that contribute to the cohesion of the dermis and epidermis) lead to the disorder referred to as junctional epidermolysis bullosa (JEB). In this disorder, there can be severe spontaneous blistering of the skin and mucous membranes. A severe form of the disease, JEB gravis, is often fatal early in life. Death occurs as a result of epithelial blistering of the respiratory, digestive, and genitourinary systems. 

Target organs of As(III)-induced effects are the cardiovascular system (myocardial depression caused by decreased contractility), gastrointestinal tract, epithelial tissues, skin, kidney, and nervous system [10,12,19]. 

Other useful criteria include the following (a) Arrangement of 4-chain disulfide bonded monomers (e.g., the pentameric structure characteristic of IgM), and carbohydrate content (b) the number of domains in the H chain (c) the presence of a secretory component (for IgA) or J chain (IgM and polymeric IgA) synthesis by a secretory immune system associated with epithelial tissues (for IgA) (d) heat lability, sensitization of skin with a relativity long latent period, prolonged persistence in skin, and a molecular weight somewhat greater than that of IgG (for IgE) (e) attachment to mast cells and basophilic leukocytes (IgE). 

Helps keep the epithelial tissues of the skin, and of the lining of the nose, throai, respiratory and digestive systems, and genitourinary tract, healthy and free of infection. 

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