The effect of zolpidem-CR on the suicide item of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia and suicidal ideation: Lessons learned.

The REST-IT study found the addition of zolpidem-controlled release (CR) provided a significant reduction in observer-rated measurement of suicidal ideation (the Columbia Suicide Severity Rating Scale) in 103 depressed outpatients with insomnia and suicidal ideation, but without significant change in a self-report measure of suicidal ideation (the Scale for Suicide Ideation). This secondary analysis of the REST-IT data examined the suicide item of another observer-rated scale, the Hamilton Rating Scale for Depression (HRSD), further clarifying the impact of insomnia-focused treatment on suicidal ideation. This analysis established a significant advantage for zolpidem-CR compared with placebo on the HRSD suicide item.

Reduced pulmonary endothelium-bound angiotensin converting enzyme activity in diabetic rabbits.

We examined the effects of diabetes on pulmonary capillary endothelial cell (EC) function in diabetic rabbits. One, three and six weeks after alloxan treatment, rabbits were anesthetized and pulmonary endothelium-bound angiotensin converting enzyme (ACE) activity was estimated from the single-pass transpulmonary hydrolysis of benzoyl-Phe-Ala-Pro (BPAP), an ACE specific substrate. ACE activity significantly decreased in 1- and 3-week diabetic rabbits and returned to control levels at 6 weeks. Capillary dilation, parenchymal hemorrhage and erythrocyte clumping were maximal in 3-week diabetic rabbits. We conclude that in the alloxan-diabetic rabbit, there are transient functional and more persistent morphological alterations.

beta-hydroxybutyrate induces acute pulmonary endothelial dysfunction in rabbits.

The authors examined the effects of high ketone body and glucose concentrations on endothelial cell (EC) function in perfused rabbit lungs. beta-Hydroxybutyrate (beta OHB), at 5 mM, decreased endothelial angiotensin-converting enzyme (eACE) activity, whereas 25 mM glucose (HG), 1 mM beta OHB, or 10 mM acetoacetate (AcAc) did not. Dry to wet weight ratios were also reduced in lungs perfused with 5 mM beta OHB, but not with AcAc. beta OHB, at 5 mM, caused massive hemorrhage and interstitial and alveolar neutrophil infiltration; AcAc only produced engorgement of septal capillaries. Thus, pulmonary EC dysfunction occurs in rabbit lungs acutely perfused with beta OHB, but not with AcAc or glucose.