Sebaceous tissue

Plasma levels of 3—5 p.g/mL are obtained two hours after adraiinistration of 200 mg ketoconazole. No accumulation in the bloodstream was noted after a 30-wk treatment with this dose. The half-life is approximately eight hours. When ketoconazole is taken with meals, higher plasma levels are obtained. Distribution studies using radioactive ketoconazole in rats show radioactivity mainly in the Hver and the connective tissue. Radioactivity is also present in the subcutaneous tissue and the sebaceous glands. After one dose of 200 mg in humans, ketoconazole is found in urine, saUva, sebum, and cenimen. Like miconazole, the mode of action is based on inhibition of the cytochrome P-450 dependent biosynthesis of ergosterol. This results in disturbed membrane permeabiUty and membrane-bound enzymes (8,10,23,25). 

Wang and coworkers first reported the use of these monomers as a novel elastomeric material for potential application in soft tissue engineering in 2002. The molar ratio of glycerol to sebacic acid they used was 1 1. The equimolar amounts of the two monomers were synthesized by polycondensation at 120°C for three days. The reaction scheme is shown in Scheme 8.1. To obtain the elastomers, they first synthesized a prepolymer and then poured an anhydrous 1,3-dioxolane solution of the prepolymer into a mold for curing and shaping under a high vacuum. 

Seborrhea in which thickened, hard, rigid, and pigmented patches occur with thickening of the dermal connective tissue layer A disease of the sebaceous glands marked by excessive discharge... 

A linearization of the steady-state concentration gradient could be demonstrated by relating the depth to the weight of the tissue, removed per piece of adhesive tape. However, large errors, especially, within the first tapes, cast doubt over these findings [127, 128], The procedure is time-consuming and artifacts, due to absorption and desorption of moisture, formulation excipients, or sebaceous lipids, are likely. 

To pass into the skin, the substance must enter through one or more of the following routes the epidermal cells, the sweat glands, the sebaceous glands, or the hair follicles. The pathway through the stratum corneum and the epidermal cells is the main avenue of penetration, as this tissue constitutes the majority of the surface area of the skin. 

Male rats treated with isophorone in the NTP (1986) study also had preputial gland carcinomas, an extremely rare finding. Analogous tissues in humans are modified sebaceous glands in the prepuce (foreskin of the penis), but it is not known whether isophorone could cause tumors in these glands or other glandular tissues in humans. 

Figure 3.9 The structure of mammalian skin (A) epidermis, (B) dermis, (C) sebaceous gland, (D) capillary, (E) nerve fibers, (F) sweat gland, (G) adipose tissue, (H) hair.

Appendageal structures commonly found within the skin are the hairs, hair follicles, associated sebaceous glands, apocrine and eccrine sweat glands, and arrector pili muscles. Hairs are formed by epidermal invaginations. These keratinized structures traverse the dermis and may extend into the hypodermis. The free part of the hair above the surface of the skin is the hair shaft, and the part deep within the dermis is the hair root, which forms an expanded knob-like structure called the hair bulb. This is composed of a matrix of epithelial cells in different stages of differentiation. Hair is composed of three concentric epithelial cell layers the outermost thin cuticle, a densely packed keratinized cortex, and a central medulla of cuboidal cells. The hair follicle consists of four major components (1) internal root sheath (internal root sheath cuticle, granular layer, pale epithelial layer) (2) external root sheath (several layers similar to the epidermis) (3) dermal papilla (connective tissue) and (4) hair matrix (comparable to the stratum basale of the epidermis). 

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