brush-border membrane of the small intestine has been characterized in the rat as well as in the human. The different hydrolyzing enzymes are activated by different types of bile salts and have distinct substrate specificities. For example, whereas the pancreatic esterase is selective for short-chain retinyl esters, the brush-border membrane enzyme preferentially hydrolyzes retinyl esters containing a long-chain fatty acid such as palmitate or stearate. Retinol enters the absorptive cells of the small intestine, preferentially in the all-trans-retinol form. Uses Common skin conditions treated by retinoids include acne and psoriasis. Retinoids are used in the treatment of many diverse diseases and are effective in the treatment of a number of dermatological conditions such as inflammatory skin disorders, skin cancers, such as bexaroten for mycosis fungoides, disorders of increased cell turnover (e.g. psoriasis), photoaging, and skin wrinkles. Isotretinoin was originally a chemotherapy treatment for certain cancers, such as leukemia. Toxicity Toxic effects occur with prolonged high intake. The specific toxicity is related to exposure time and the exposure concentration. A medical sign of chronic poisoning is the presence of painful tender swellings on the long bones. Anorexia, skin lesions, hair loss, hepatosplenomegaly, papilloedema, bleeding, general malaise, pseudotumor cerebri, and death may also occur. Chronic overdose also causes an increased lability of biological membranes and of the outer layer of the skin to peel. Recent research has suggested a role for retinoids in cutaneous adverse effects for a variety of drugs including the antimalarial drug proguanil. It is proposed that drugs such as proguanil act to disrupt retinoid homeostasis. Systemic retinoids (isotretinoin, etretinate) are contraindicated during pregnancy as they may cause CNS, cranio-facial, cardiovascular and other defects. See also Hypervitaminosis A References The Pharmacological Basis of Therapeutics, 10th Edition, Goodman & Gilman. Clinical Pharmacology, P.N. Bennett & M.J. Brown. External links