The emergence of oral and topical retinoids was a major advance in the clinical management of acne vulgaris. However, the benefits of these agents were somewhat limited by the degree of side effects caused by these drugs. Over the last 15 years, researchers have sought compounds that can provide the manifold therapeutic benefits obtained with tretinoin and isotretinoin while minimizing the potential for irritation and other unwanted effects. Adapalene, a naphthoic-acid derivative, is one result of this search, and it serves as an example of rational drug development: the formulation of a novel substance with specific pharmacological properties and clinical objectives in mind. These goals included enhancing stability, enhancing anti-inflammatory effects, maintaining effectiveness and minimizing cutaneous irritation. This paper reviews the history of the development of adapalene, its unique physical and biochemical properties, and the pharmacological studies that demonstrate a wide range of retinoid-receptor, genetic and anti-inflammatory effects, all of which contribute to the therapeutic efficacy and improved tolerability of adapalene observed in the clinical use of this agent for the treatment of acne.

When confluent cultures of the transformed human keratmocyte hne SV-K14 are shifted to serum-free medlurn the cells achieve, wlthm 4 days, the ablhty to synthesize a cormfied envelope after challenge with the Caz+ lonophore A23187 During these 4 days the enzyme transglutammase (EC 2 3 2 13), which catalyses the cross-hnkmg of different envelope precursor protems, IS partially transferred from the cytosohc pool mto the plasma membrane The association of the enzyme with the plasma membrane proves to be an essential step m the envelope formatlon smce a du-ect correlation between plasma membrane-bound transglutammase and envelope competence IS observed Retmolds block the Insertion of the enzyme and therefore prevent envelope formatlon Transglutammase Plasma membrane

No abstract

Deamination of 4‐aminobutyrate by mammalian or bacterial 4‐aminobutyrate aminotransferases involves the abstraction of the pro‐S hydrogen on C‐4 of 4‐aminobutyrate. Decarboxylation of L‐glutamate by rat brain glutamate decarboxylase occurs with retention of configuration. Inhibition of this enzyme by (S)‐4‐aminohex‐5‐ynoic acid involves the abstraction of the proton at C‐4 of the inhibitor. On the basis of this finding, we postulate the existence of an abnormal reaction of glutamate decarboxylase in which the proton at C‐4 of (S)‐4‐aminohex‐5‐ynoic acid is removed in a manner similar to the one which normally occurs in enzymatic transaminations of L‐amino acids. This reaction is presumably facilitated by the acetylenic group adjacent to the eliminated proton.

No abstract