Our results suggest that the chronic administration of mood stabilizers may produce a neurotrophic effect mediated by the upregulation of BDNF in the rat brain.

Intracellular calcium concentrations ([Ca++]i) in blood platelets from 11 depressed patients and 11 healthy controls were investigated. The resting [Ca++]i of platelets from depressed patients was 69.4 +/- 2.9 nM while that from controls was 74.6 +/- 4.0 nM. Serotonin (5-HT), at a concentration of 10 microM, increased [Ca++]i by 129.2 +/- 3.9 nM in platelets from depressed patients, which was significantly greater than that found in platelets from control subjects (105.2 +/- 6.0 nM). Norepinephrine (NE) 100 microM increased [Ca++]i by 46.1 +/- 7.1 nM in platelets from depressed patients, and by 38.6 +/- 6.1 nM in platelets from controls, respectively. These results indicate that 5-HT2 receptor function in platelets of depressed patients is enhanced, and support the hypothesis of hypersensitivity of 5-HT2 receptors in affective disorders.

There are a number of investigations which indicate the important relationship between depression and cytokines. In this study, we investigated plasma interleukin (IL)-1β, IL-6, soluble IL-2 receptor (sIL-2R) and tumor necrosis factor (TNF)-α of depressed patients whose clinical evaluation was performed by the Hamilton Rating Scale for Depression (HAM-D) and the Profile of Mood States (POMS). They were compared with those of the control subjects, and before and after treatment with antidepressants. Before the treatment, plasma IL-1β, IL-6, sIL-2R and TNF-α of the patients were not significantly different from those of the control subjects. sIL-2R was positively correlated with the POMS-tension-anxiety subscale and tended to have a positive correlation with HAM-D. After pharmacotherapy, TNF-α levels of the depressed patients increased, without any relationship between the change in the HAM-D or the POMS and the change in TNF-α. These results suggest that the plasma sIL-2R concentration is associated with mood state, and that the plasma TNF-α concentration is increased after pharmacotherapy in Japanese depressed patients.

No abstract

Although haloperidol is mainly used for the medical treatment of delirium in cancer patients, there are no universally accepted guidelines for its usage. We accordingly assessed the usefulness in managing delirium of a haloperidol treatment regimen in ten delirious cancer patients. The results of this preliminary study suggest that, in the management of delirium, appropriate usage of haloperidol on the first day is important as it affects the dosage thereafter.

We investigated plasma dehydroepiandrosterone sulfate (DHEAS) and cortisol levels in 12 patients with unipolar depression and 11 matched normal controls. The depressed patients showed significantly higher values of plasma DHEAS and cortisol than the controls. After 4 weeks of treatment with antidepressants (mainly clomiplamine), the high plasma DHEAS levels recovered. This finding showed the possible relationship between plasma DHEAS levels and depression, as well as cortisol levels.

No abstract

We investigated neurotrophic effects of interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on cultured sympathetic neurons obtained from mouse superior cervical ganglia. After 1 day of culture with physiological concentrations of mouse recombinant IL-3 and GM-CSF, the numbers of process-bearing neurons were increased. Maximum responses were elicited by 10 U/ml IL-3 and 1 U/ml GM-CSF, which were equivalent to the action of a submaximal dose (5 ng/ml) of nerve growth factor (NGF). The effects of IL-3 and GM-CSF were completely blocked by their corresponding antibodies, but not by anti-NGF, indicting their action is specific and completely independent of NGF. IL-3 and, to a lesser extent, GM-CSF were also able to protect NGF-differentiated neurons from apoptotic cell death caused by NGF withdrawal. The mitogen-activated protein (MAP) kinase signal transduction pathway is known to be involved in action of IL-3 and GM-CSF on hemopoietic cells, and thus we examined the participation of this pathway in the neurotrophic activities of IL-3 and GM-CSF. IL-3 and GM-CSF stimulation of the differentiated neurons was found to result in a rapid elevation of MAP kinase activity, and PD98059, an inhibitor of MAP kinase kinase activity, blocked both the neuritogenic and neuroprotective effects of IL-3 and GM-CSF. Immunocytochemical studies showed that IL-3 and GM-CSF receptors were present on the differentiated neurons. Thus, IL-3 and GM-CSF appear to be able to stimulate sympathetic nerve growth, via specific cytokine receptors on neurons, which lead to activation of the MAP kinase pathway that then mediates the observed neurotrophic effects.