Action of topically applied arachidonic acid on the skin of patients with psoriasis.

Concentrations of arachidonic acid ranging from 0.1% to 2% were applied under occlusive dressings to psoriatic plaques in 45 patients. Alleviation of the clinical symptoms of psoriasis including complete clearing in some cases was obtained with the use of 0.5% to 2% arachidonic acid applied under occlusion every 24 to 48 hours five to seven times. Histologic examination showed polymorphonuclear leukocytes penetrating into the stratum corneum and formation of microabscesses or wide-spread accumulations of polymorphonuclear leukocytes in the stratum corneum, with its eventual destruction. The parakeratotic horny layer became detached; this was followed by restoration of the granular layer and an apparently normal stratum corneum. While arachidonic acid metabolites can be proinflammatory and proproliferative, they may also be important in the healing process for psoriasis.

Treatment of psoriasis of the scalp with coal tar gel and shampoo preparations.

Psoriatic lesions on the scalp are cosmetically troublesome and present problems for therapy, particularly over a long-term period. A gel containing refined coal tar in solution (psoriGel) was effective in clearing or markedly improving psoriasis of the scalp in 83 percent of 112 patients. The study population included thirty-five patients who were unresponsive to other therapies. The treatment regimen described here used tar gel for five days, vegetable oil soaking for the sixth day, and no treatment on the seventh day. This procedure reduced considerably the tendency of tar gel to cause drying of the skin. Fifty percent of the patients remained in remission for about three months using a nontar shampoo. However, using a tar shampoo (Ionil T), the median remission time was extended to over eight months with 30 percent of the patients still in remission thirteen months later. No adverse reactions were reported.

7 alpha-Alkyltestosterone derivatives: synthesis and activity as androgens and as aromatase inhibitors.

The 7 alpha-ethyl,propyl,butyl,3'-t-butoxypropyl,allyl,3'-hydroxypropyl 17-acetate, and 3'-chloropropyl 17-acetate derivatives of testosterone and the 7 alpha-3'-t-butoxypropyl, 3'-hydroxypropyl,3'-acetoxypropyl,3'-bromoacetoxypropyl, 3'-chloropropyl, and 2'-oxo-3'-bromopropyl derivatives of 4-androstene-3,17-dione were synthesized. The testosterone derivatives were found to lose androgenic and anabolic activity rapidly as the size of the group at the 7 position increased. Many of the compounds were tested as inhibitors of aromatase. The 17-keto compounds were more active than the corresponding alcohols and the enzyme was found to tolerate at least the bulk of a hydroxypropyl group at the C-7 alpha position.

Synthesis and antitumor activity of 5'-phosphates and cyclic 3',5'-phosphates derived from biologically active nucleosides.

Syntheses and biological activities of 12 N6-substituted adenosine 5'-phosphates and 15 cyclic 3',5'-phosphates are described. Included among these are the cyclic phosphates of the naturally occurring anticodon adjacent modified nucleosides, N6-(delta2-isopentenyl)adenosine and N-(purin-6-ylcarbamoyl)-L-threonine ribonucleoside. Also reported in this paper are the 5'-phosphates and cyclic phosphates of the cytokinins, N6-benzyladenosine, kinetin ribonucleoside, 3-(chloro-trans-2-buten-2-yl)adenosine,6-o-chlorophenylureidopurine ribonucleoside, and 6-allylureidopurine ribonucleoside. The 5'-nucleotides were prepared by direct phosphorylation of the corresponding ribonucleosides with POCl3 and triethyl phosphate. These compounds were converted to the cyclic 3',5'-phosphates by cyclization of the corresponding 5'-nucleotides with dicyclohexylcarbodiimide. Comparison of the cytotoxicity of the ribonucleosides with their 5'-nucleotides and cyclic 3',5'-nucleotides showed that some of the 5'-phosphates and cyclic phosphates were almost as active as the parent nucleosides. The 5'-nucleotides and the cyclic phosphates were more soluble than the parent nucleosides. The cyclic 3',5'-nucleotides were examined as alternate activators of cAMP-dependent protein kinase from beef heart. While all of the analogs studied showed some activity toward this enzyme, several compounds were more effective than cAMP itself. The analogs were also tested as substrates for cyclic 3',5'-nucleotide phosphodiesterase from beef heart. The N6-alkyl-cAMP analogs were poor substrates for the enzyme, while N6-carbamoyl-cAMP derivatives were inert toward this enzyme. These compounds did not inhibit the phosphodiesterase. Some of the cyclic phosphates exhibited marginal effect in the inhibition of glycogen synthesis in skin slices.

Synthesis and biological activity of some ethers of testosterone. Implications concerning the biological activity of esters of testosterone.

The benzyl (2), allyl (4), propyl (10), 3-hydroxypropyl (12), 2,3-dihydroxypropyl (11), 4 pentenyl (7), and pentyl (8) ethers of testosterone were synthesized. Compounds 2, 4, 7, 8, 10, and 12 were found to be almost devoid of anabolic or androgenic activity in a modified Hershberger Assay, but 2,4,10, and 12 were found to be effective inhibitors of testosterone 5alpha-reductase from human skin. These findings suggest that esters of testosterone and of 19-nortestosterone must hydrolyze before interacting with the hormonal receptors, but that the esters may competitively compete with the parent alchohols for interaction with enzymes. The latter effect may shift the distribution of metabolites of the esters relative to the alchohols and thus influence the pharmacological effect of these compounds.