Association of cyclosporine and 311 nM UVB in the treatment of moderate to severe forms of psoriasis: a new strategic approach.

Psoriasis is a T-lymphocyte mediated autoimmune disease. The response to therapies targeting T-lymphocytes suggest that the latter is a key cell in the pathogenesis of the disease. Cyclosporine (CsA) inhibits the proliferation and the IL-2 dependent expansion of T-lymphocytes. Ultraviolet radiation is an effective treatment for psoriasis. Several studies have demonstrated a significant improvement of the therapeutic response when narrow-band radiation is issued by TL-01 fluorescent lamp compared to broad- band UVB issued by other fluorescent sources. The effects of UVB on the immune system appear to be limited to the cell-mediated compartment of the immune response. In order to reduce the cumulative dose of UVB and limit the toxicity of drugs in the therapy of psoriasis, phototherapy with UVB has been used as treatment in association with other standard therapies. The purpose of the study is to evaluate, in patients with moderate to severe psoriasis a combined therapy with Cyclosporine A and 311 nm UVB phototherapy.

Solvation of the Carbonyl Compound as a Predominant Factor in the Diastereofacial Selectivity of Nucleophilic Addition.

Temperature-dependent selectivity in nucleophilic additions is affected by the solvent. The inversion temperature (marked with arrows in the graph) that appears in the nonlinear Eyring plots of ln (anti/syn) versus temperature for the addition of butyllithium to an O-protected alpha-hydroxy aldehyde 1 does not depend on nucleophiles (nBuLi (black triangle), tBuLi (*)), but on the solvent. Its value can be obtained from a plot of the (13)C NMR chemical shift of C=O versus temperature. TBDMS=tBuMe(2)Si.

Synthesis and physicochemical, biological, and pharmacological properties of new bile acids amidated with cyclic amino acids.

New analogs of cyclic amino acid-conjugated bile acids were synthesized, and their physicochemical and biological properties were compared with those of natural analogs. Ursodeoxycholic acid was amidated with D-proline, L-proline, 4-hydroxy-L-proline, and 4-methoxy-L-proline. Hyocholic and hyodeoxycholic acids were amidated with L-proline. The physicochemical properties were similar to those of the natural analogs. All of them were highly stable toward enzymatic C-24 amide bond hydrolysis and 7-dehydroxylation. Their transport, metabolism, and effect on biliary lipid secretion were evaluated in bile fistula rat after intravenous infusion. All the analogs were secreted in bile unmodified. The 4-methoxy-L-proline derivative produced the highest secretion rate, much higher than those of all the other natural and synthetic analogs. This was associated with a selective reduction of cholesterol secretion with normal phospholipid secretion and choleresis. When coinfused, all the analogs were able to prevent the hepatotoxicity induced by intravenous taurochenodeoxycholic acid, as revealed by normal choleresis, alkaline phosphatase, and lactate dehydrogenase values in bile. Considering the overall data, 4-methoxy-L-proline, 4-hydroxy-L-proline, and L-proline derivatives of ursodeoxycholic acid were more potent than the natural analogs.