Family history of depression and therapeutic outcome: findings from STAR*D.

Objective: It is unclear whether a positive family history of depression affects the clinical presentation or effectiveness of treatment for major depressive disorder (MDD). We aimed to determine whether depressed patients with a positive family history of depression differed from those without in terms of baseline sociodemographic and clinical characteristics, including concurrent comorbid conditions and treatment outcome with citalopram in a large, multicenter effectiveness trial.

Method: Clinical outcome and sociodemographic information were collected on 2876 participants with DSM-IV MDD enrolled from July 2001 through April 2004 in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.

Factors that differentiate early vs. later onset of major depression disorder.

This report explores the relationship between age of first onset of major depression and other demographic and clinical features in the first 1500 patients entering the Sequenced Treatment Alternative to Relieving Depression (STAR*D) study. Outpatients, 18-75 years of age, with nonpsychotic major depressive disorder (MDD) from either primary care or psychiatric practices constitute the population. Age of onset was defined at study intake by asking patients to estimate the age at which they experienced the onset of their first major depressive episode.

Effects of inhibition of poly(adenosine diphosphate-ribose) synthase on acute cardiac allograft rejection.

Background: Nitric oxide synthase (NOS)-2 is expressed during acute cardiac allograft rejection in association with death of heart muscle cells. The nuclear enzyme poly(adenosine diphosphate [ADP]-ribose) synthase (PARS) is activated by agonists such as NO and peroxynitrite, which cause single-strand DNA breaks; PARS, in turn can promote both necrosis and apoptosis. To investigate the hypothesis that NO produced by NOS-2 in cardiomyocytes activates PARS and contributes to heart muscle cell death by apoptosis, experiments were performed using a heterotopic rat abdominal heart transplant model and cytokine-stimulated heart muscle cells in tissue culture.

Metabolic and functional protection by selective inhibition of nitric oxide synthase 2 during ischemia-reperfusion in isolated perfused hearts.

Background: Drugs that selectively block nitric oxide synthase (NOS) 2 enzyme activity by inhibiting dimerization of NOS2 monomers have recently been developed.

Methods And Results: To investigate whether selective inhibition of NOS2 is cardioprotective, rats were pretreated for 2 days with BBS2, an inhibitor of NOS2 dimerization, at 15 mg/kg SC. Isolated buffer-perfused hearts from treated (n=9) and control (n=7) hearts were subjected to 20 minutes of ischemia followed by 60 minutes of reperfusion.

The effect of selective inhibition of cyclooxygenase (COX)-2 on acute cardiac allograft rejection.

Background: Using a rat (Lewis-Wistar Furth) abdominal heterotopic transplantation model, we reported previously that the expression of cyclooxygenase (COX)-2 is increased in parallel with that of nitric oxide synthase (NOS)-2 during cardiac allograft rejection.

Methods: To investigate effects of COX-2 inhibition in this model, allograft recipients were treated orally (PO) with 5 mg/kg per day of the tetra substituted furanone selective COX-2 inhibitor 5,5-dimethyl-3-(3 fluorophenyl)-4-(4 methylsulfonal) phenyl-2 (5H)-furanone (DFU) in 1% methyl cellulose solution.

Results: In the treated animals, allograft survival was increased from 6.