[Short-course isoniazid and rifampin compared with isoniazid for latent tuberculosis infection: a randomized clinical trial].

Introduction: The aim of this study was to compare the adherence to, and side effects of a 3-month short-course treatment for latent tuberculosis infection as compared to the standard 6-month course.

Methods: Prospective, comparative, randomized, open trial including patients with a positive tuberculin skin test and appropriate criteria for treatment in accordance with the CDC guidelines, and excluding patients with HIV infection. Group I (6H) was assigned to isoniazid 300 mg per day for 6 months and Group II (3HR) was assigned to isoniazid 300 mg per day plus rifampin 600 mg per day for 3 months.

A medicinal-chemistry-guided approach to selective and druglike sigma 1 ligands.

Based on a medicinal-chemistry-guided approach, three novel series of druglike cycloalkyl-annelated pyrazoles were synthesized and display high affinity (pKi>8) for the sigma1 receptor. Structure-affinity relationships were established, and the different scaffolds were optimized with respect to sigma1 binding and selectivity versus the sigma2 receptor and the hERG channel, resulting in selective compounds that have Ki values (for sigma1) in the subnanomolar range. Selected compounds were screened for cytochrome P450 inhibition (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4), metabolic stability (rat and human liver microsomes), and cell-membrane permeability (Caco-2).