Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.

1. The effects of two reversible, predominantly monoamine oxidase-A (MAO-A) inhibitors, moclobemide (150 mg three times daily) and toloxatone (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects. 2. After 7 days of moclobemide/toloxatone/placebo administration subjects were hospitalized for 24 h on day 8. Blood samples were drawn every 2 h for determination of plasma noradrenaline (NA), 3,4-dihydroxyphenylglycol (DHPG), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA). Urine was collected for measurements of normetanephrine and 3-methoxytyramine excretion. Psychometric performance (short- and long-term memory, critical flicker fusion frequency, choice reaction time) and subjective feelings were assessed before each drug intake (in the morning, at noon, in the evening). 3. Compared with placebo, both reversible monoamine oxidase inhibitors decreased the plasma concentration of DHPG and HVA. The overall fall in DHPG (AUC from 0 to 24 h) was 44% during moclobemide and 12% during toloxatone (P less than 0.001) and the overall decrease in HVA was 38% and 20% (P less than 0.005) on moclobemide and toloxatone, respectively. 4. Before the next drug intake, MAO-A inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with toloxatone. 5. Moclobemide, but not toloxatone, exerted a moderate, but significant inhibition of the deamination of 5-hydroxytryptamine (5-HT) as judged by the fall in plasma 5-HIAA concentration. Neither drug influenced plasma NA concentration. 6. A significant rise in urinary excretion of normetanephrine was observed on moclobemide and to a lesser extent on toloxatone. The urinary excretion of 3-methoxytyramine was significantly raised by moclobemide but not by toloxatone. 7. Neither moclobemide nor toloxatone altered memory function, vigilance, subjective feelings or sleep characteristics of the subjects.     

Ethics of asking trauma-related questions and exposing participants to arousal-inducing stimuli.

This study examined ethical concerns related to exposing participants with childhood victimization histories to both trauma-specific and non-trauma-specific stimuli. We asked participants questions about childhood victimization experiences and exposed participants to a negatively-arousing experimental condition. Following each of these procedures and at a one-week follow-up session, participants completed a measure designed to asses their reactions to participation. The measure included several questions to assess reactions including questions about distress, benefit, and willingness to participate in the study again. Overall, participants reported low levels of distress and described their participation experience as interesting, enjoyable, and somewhat beneficial. Participants also indicated that they would be willing to participate in the study again with the knowledge of what participation was actually like. Participants with childhood trauma histories and PTSD symptoms reported more distress during the childhood maltreatment screening compared to other participants. However, the level of distress they experienced was mild and transitory. Our findings add to the emerging data indicating that individuals find their participation in trauma-related research to be a positive experience overall, rather than a harmful one.     

The health and wellbeing of informal caregivers: a review and study program

Abstract: Informal caregivers are the families and other unpaid caregivers in the home who support people of all ages with severe and chronic mental or physical disabilities. Home care of this sort has been increasing over the past 30 years because of the reduced number of beds in hospitals and nursing homes and increased outpatient and community care. Moreover, with an aging population and increasing rates of disability, the demand for family caregiving will continue to rise. This has important implications for the development of health, community service and social policy. At the same time, however, very little is known about the impact such changes are having on the caregivers of various ages and in various circumstances. The Victorian Health Promotion Foundation is funding a research and intervention program in Melbourne to promote wellbeing and prevent ill-health in caregivers.     

Structure-activity relationship of macrocyclic and linear gadolinium chelates: Investigation of transmetallation effect on the zinc-dependent metallopeptidase angiotensin-converting enzyme

Transmetallation between commercially available solutions of gadolinium (Gd) chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was investigated. In vitro, the strongest inhibitions were observed for the linear Gd complexes, Gd diethylene-triamine pentaacetic acid (DTPA) bis-methylamide (BMA) (IC₅₀ = .016 ± .006 mmol/1) and Gd-DTPA (IC₅₀ = .350 ± .034 mmol/1). The two macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of DTPA-BMA because the addition of Zn²⁺ in the same quantities suppresses their inhibitory effects. In vivo, these two solutions of linear Gd chelates significantly inhibited ACE activity (Gd-DTPA: 67 ± 9% versus baseline; and Gd-DTPA-BMA: 73 ± 2% versus baseline at the clinical dose of .1 mmol/kg), whereas no significant effect was observed for the two macrocyclic chelates Gd-DOTA and Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free ligand or Ca chelate (to decrease Gd³⁺ release) in the case of linear Gd chelate may have deleterious biologic consequences.     

Growth hormone benefits children with 18q deletions

Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long-term outcomes for the treated individuals.