Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

Background: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS).

Objective: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients.

Setting: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis.

Effect of chronic lithium treatment on the turnover of alpha2-adrenoceptors after chemical inactivation in rats.

One of the most effective psychotherapeutic agents in the treatment of bipolar disease is lithium. Chronic lithium treatment affects some signal transduction mechanisms such as cAMP, cGMP, inositol 1,4,5 P(3), Gi protein, protein kinase C and can also modify gene expression in rat brain. In a previous study, we observed a greater inhibitory effect of lithium on cAMP production after blockade of alpha(2)-adrenoceptors in rat cerebral cortex.

Effect of alpha 2-adrenoceptor blockade on lithium action in the rat brain.

The inhibitory effect of different concentrations of lithium (0.15-10 x 10(-3) M) on cAMP production induced by isoprenaline (1 x 10(-4) M) after the blockade of alpha(2)-adrenoceptors in the rat cerebral cortex was investigated. Low lithium concentrations (0.

Effects of phospholipid vesicles (liposomes) on cAMP levels in the rat cerebral cortex.

We studied the effects of two types of liposomes (cholate-free liposomes and cholate-containing liposomes) on control (in the presence of 3-isobutyl-1 methyl xanthine [IBMX], a phosphodiesterase inhibitor) and stimulated (IBMX plus isoprenaline) cyclic 3',5'-adenosine monophosphate (cAMP) accumulation in slices of rat cerebral cortex. Our purpose was to examine whether or not liposomes with different lipid constituents modify levels of cAMP in vitro. Liposomes at low concentrations had a significant inhibitory effect on cAMP accumulation in brain tissue.

Novel azo derivatives as prodrugs of 5-aminosalicylic acid and amino derivatives with potent platelet activating factor antagonist activity.

This paper describes the synthesis of a series of azo compounds able to deliver 5-aminosalicylic acid (5-ASA) and a potent platelet activating factor (PAF) antagonist in a colon-specific manner for the purpose of treating ulcerative colitis. We found it possible to add an amino group on the aromatic moiety of our reported 1-[(1-acyl-4-piperidyl)methyl]-1H-2-methylimidazo[4,5-c]pyridine derivatives or on British Biotech compounds BB-882 and BB-823 maintaining a high level of activity as PAF antagonist. A selected compound UR-12715 (49c) showed an IC(50) of 8 nM in the in vitro PAF-induced aggregation assay, and an ID(50) of 29 microg/kg in the in vivo PAF-induced hypotension test in normotensive rats.