Dermis effect

It has been established that artificial skin regenerates the dermis effectively and therefore its use leads to complete inhibition of scar formation in full-thickness skin wounds. The regeneration is partial however, skin adenexa (hair follicles, sweat glands) are not recovered. 

There are hundreds of topical steroid preparations that are available for the treatment of skin diseases. In addition to their aforementioned antiinflammatory effects, topical steroids also exert their effects by vasoconstriction of the capillaries in the superficial dermis and by reduction of cellular mitosis and cell proliferation especially in the basal cell layer of the skin. In addition to the aforementioned systemic side effects, topical steroids can have adverse local effects. Chronic treatment with topical corticosteroids may increase the risk of bacterial and fungal infections. A combination steroid and antibacterial agent can be used to combat this problem. Additional local side effects that can be caused by extended use of topical steroids are epidermal atrophy, acne, glaucoma and cataracts (thus the weakest concentrations should be used in and around the eyes), pigmentation problems, hypertrichosis, allergic contact dermatitis, perioral dermatitis, and granuloma gluteale infantum (251). 

Jessner s Solution has been used for over 100 years as a therapeutic agent to treat hyperkera-totic epidermal lesions [1]. This superficial peeling agent constitutes a mixture of salicylic acid, resorcinol, and lactic acid in 95% ethanol. Jessner s solution causes loss of corneocyte cohesion and induces intercellular and intracellular edema. Jessner s typically induces wounding to the level of the papillary dermis. Historically, resorcinol (a key component of Jessner s peels) was used in concentrations of 10-50% in the early twentieth century. High concentrations of resorcinol were associated with side effects such as allergic contact dermatitis, irritant contact... 

Epidermal growths such as actinic keratosis, lentigines or thin seborrheic keratoses can all be treated effectively with 25-35% TCA peels. Thicker epidermal growths or growths involving the dermis will be more resistant to treatment such as hypertrophic actinic keratoses and thicker seborrheic keratoses and may even be resistant to a medium-depth peel. Resistant lesions many times are best treated with a combination of a medium-depth chemical peel and other modalities such as manual dermasanding or CO, laser. 

Salicylic acid has a keratolytic effect, thus eliminating superficial pigmented keratinocytes and stimulating cells turnover. This superficial peeling allows TCA to act a low concentration to remove pigmented keratinocytes through papillary dermis (see Fig. 14.12). 

Superficial chemical peels, including salicylic and glycolic acids, and Jessner s peels target the stratum corneum to the papillary dermis. These agents can be safely used to facilitate the resolution of PIH (Figs. 16.2,16.3,16.4 and 16.5). To assess for variability in response and limit further PIH, when possible, chemical peels should be initiated at the lower concentrations and titrated to higher concentrations if necessary to increase efficacy while minimizing side effects (see Darker Skin Section). 

Ointments are the most effective formulations for psoriasis because they have an occlusive oily phase that conveys a hydrating effect and enhances penetration of the corticosteroid into the dermis. They are not suited for use in the axilla, groin, or other intertriginous areas where maceration and folliculitis may develop secondary to the occlusive effect. 

Absorption Across the Skin. An aqueous carrier may be used for a variety of dermal products. In fact, carriers can be designed to limit the transportation of the penetration of the active ingredient (such as an insect repellent), if the desired effect is to keep the activity on the surface of the skin. Once again, however, only those materials that are dissolved will be available for penetration across the skin to gain access to the systemic circulation. For almost all chemicals in or about to enter commerce, dermal penetration is a passive process. The relative thickness of the skin makes absorption (into the systemic circulation) slower than the absorption across the GI or pulmonary barriers. This is compounded by the fact that the stratum comeum ftmction is to be impervious to the environment. One of the skin s major functions is protection from infection. Once a chemical penetrates into the dermis, it may partition into the subcutaneous fat. Essentially, absorption across the skin is a two-step process with the first being penetration and deposition into the skin and the second being release from the skin into the systemic circulation. The pattern of blood levels obtained via dermal penetration is generally one with a delayed... 

Tandon et al. (1975) applied daily dermal applications of 132.5 mg thorium/kg body weight/day (15 nCi/kg/day = 555 Bq/kg/day), 265 mg thorium/kg body weight/day (29 nCi/kg/day = 1073 Bq/kg/day), or 529 mg thorium/kg body weight/day (58 nCi/kg/day = 2146 Bq/kg/day) to the lateroabdominal and scrotal areas of rats for 15 days. The thorium was administered to skin (hair was clipped) as thorium nitrate, and the area remained uncovered for the duration of treatment. Mild hyperkeratinization of the lateroabdominal skin was found at all exposure levels. At the highest exposure level, mild acanthosis and thickening of the epithelial lining of the lateroabdominal skin were seen. At this level, mild acanthosis, swollen collagen fibers, and foamy dermis were found in the scrotal skin. The value of 15 nCi/kg/day is a less serious LOAEL, and the exposure level of 58 nCi/kg/day is a serious LOAEL for dermal effects in the rat. These values are reported in Table 2-3. 

Effects on the skin were observed in rats treated dermally with 40 mg nickel/kg/day as nickel sulfate for 15 or 30 days (Mathur et al. 1977). The effects included distortion of the epidermis and dermis after 15 days and hyperkeratinization, vacuolization, hydropic degeneration of the basal layer, and atrophy of the epidermis at 30 days. Biochemical changes in the skin (enzymatic changes, increased lipid peroxidation, and an increase in the content of sulfhydryl groups and amino nitrogen) were observed in... 

Nickel sensitivity has also been induced in guinea pigs by skin painting or intradermal injection (Wahlberg 1976 Zissu et al. 1987) and in mice by dermal contact (Siller and Seymour 1994). Dermal effects in animals after dermal exposure to nickel included distortion of the epidermis and dermis, hyperkeratinization, atrophy of the dermis, and biochemical changes (Mathur et al. 1977, 1988). 

The incidence of adverse effects with hydroquinone increases in proportion to its concentration. A relatively common side effect is local irritation, which may actually exacerbate the discoloration of the skin being treated. Allergic contact dermatitis occurs less commonly. A rare but more serious complication is exogenous ochronosis, in which a yellow-brown pigment deposited in the dermis results in blue-black pigmentation of the skin that may be permanent. 

Stoker, P.W., M.R. Plasterer, R.L. McDowell, R. Campbell, S. Fields, R. Price, C. Muehle, W.R. West, G.M. Both, J.R. Larsen, and M.L. Lee. 1984. Effects of coal-derived tars on selected aquatic and mammalian organisms. Pages 1239-1257 in M. Cooke and A.J. Dermis (eds.). Polynuclear Aromatic Hydrocarbons Mechanisms, Methods and Metabolism. Battelle Press, Columbus, OH. 

Some pharmacokinetic properties of the commonly used amide local anesthetics are summarized in Table 26-2. The pharmacokinetics of the ester-based local anesthetics have not been extensively studied owing to their rapid breakdown in plasma (elimination half-life < 1 minute). Local anesthetics are usually administered by injection into dermis and soft tissues around nerves. Thus, absorption and distribution are not as important in controlling the onset of effect as in determining the rate of offset of local analgesia and the likelihood of CNS and cardiac toxicity. Topical application of local anesthetics (eg, transmucosal or transdermal) requires drug diffusion for both onset and offset of anesthetic effect. However, intracavitary (eg, intra-articular, intraperitoneal) administration is associated with a more rapid onset and shorter duration of local anesthetic effect. 

Benzoyl peroxide is an effective topical agent in the treatment of acnevulgaris. It penetrates the stratum corneum or follicular openings unchanged and is converted metabolically to benzoic acid within the epidermis and dermis. Less than 5% of an applied dose is absorbed from the skin in an 8-hour period. It has been postulated that the mechanism of action of benzoyl peroxide in acne is related to its antimicrobial activity against P acnes and to its peeling and comedolytic effects. 

The unique form of needle-free injection of powders into the epidermis or mucosa has been developed by researchers at the University of Oxford and Powderject Pharmaceuticals PLC (now PowderMed Ltd., United Kingdom). Drugs in microparticulate form are accelerated to sufficient velocities to enter the skin or mucosa and achieve a therapeutic effect (Burkoth et al. 1999). Provided the drug particles are sufficiently small to avoid skin lesions and pain, the concept has been shown to be clinically effective, pain-free, and applicable to a range of therapies. Use is pain-free because the penetration depth of the particles is typically less than 100 J,m into the epidermis, and thus the sensory nerve endings lying in the papillary dermis usually are not excited (Fig. 8.15). 

---