Down-regulation of PKC alpha by lithium in vitro.

In recent years, research aimed at the elucidation of lithium's molecular mechanisms has focused on signal transduction pathways. This research has demonstrated that lithium has multiple effects on the phosphoinositide turnover signaling system. We have previously demonstrated that chronic (but not acute) in vitro exposure of HL60 cells to 1 mM lithium reduces both receptor and phorbol-ester-mediated Na+/H+ activity without affecting agonist-induced increases in intracellular Ca2+ or phosphoinositide breakdown, findings which suggest an attenuation of protein kinase C (PKC) function.

Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro.

Valproic acid (VPA) is a fatty acid antiepileptic with demonstrated antimanic properties, but the molecular mechanism or mechanisms underlying its therapeutic efficacy remain to be elucidated. In view of the increasing evidence demonstrating effects of the first-line antimanic drug, lithium, on protein kinase C (PKC), we investigated the effects of VPA on various aspects of this enzyme. Chronic exposure (6-7 days) of rat C6 glioma cells to "therapeutic" concentrations (0.

Co-storage in large 'dense-core' vesicles of dopamine and cholecystokinin in rat striatum.

The subcellular localization of cholecystokinin in the striatum--an area where a high density of cholecystokinin containing terminals has been demonstrated--was studied using biochemical techniques. Cholecystokinin containing vesicles were partially purified using iso-osmotic Ficoll gradients. As judged from their size and their buoyant density in isopycnic gradients, cholecystokinin containing vesicles represent large 'dense-core' vesicles.

A pharmacodynamic study of the alpha 2-adrenergic receptor antagonist ethoxyidazoxan in healthy volunteers.

Ethoxyidazoxan, a potent and highly selective alpha 2-adrenergic receptor antagonist, was administered intravenously to six healthy male volunteers in a double-blind, placebo-controlled, dose-rising design. Doses of 6 micrograms/kg and 8 micrograms/kg infused intravenously over 30 minutes produced significant elevations of plasma norepinephrine and body temperature and inhibited norepinephrine-induced platelet aggregation. Central activity was shown by reversal of the slowing of saccadic eye movements and an increase in saccade peak velocity at the higher dose.

Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine.

Background: This study examined the effect of long-term (mean, 19 months) treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of several neuropeptides and monoamine metabolites in children and adolescents with obsessive-compulsive disorder.

Methods: The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after long-term treatment with clomipramine.

Results: Treatment resulted in significant decreases in CSF levels of corticotropin-releasing hormone (mean +/- SD, 175 +/- 32 vs 152 +/- 25 pmol/L, P < .

Receptor-mediated internalization of angiotensin II in bovine adrenal medullary chromaffin cells in primary culture.

Binding and internalization of angiotensin II (AII) were studied on bovine adrenal medullary cells in primary culture. Binding of [125I]AII was reversible, saturable, specific and showed high affinity. AII was found to be internalized by bovine adrenal medullary cells.

Interaction of serotonin- and dopamine-related neurotoxins with "serotonin binding proteins" in bovine frontal cortex.

Binding of [3H]serotonin and [3H]dopamine to serotonin-binding proteins (SBP) from soluble extracts of bovine frontal cortex is increased by Fe2+. This group recently attributed this effect of Fe2+ to its ability to enhance the oxidation of [3H]serotonin and [3H]dopamine in the presence of dissolved molecular oxygen, and to the ability of the formed oxidation products to bind covalently to cysteine residues of SBP. In this study it is shown that the binding of both ligands is potently inhibited by dopamine as well as by several catecholamine-and serotonin-related neurotoxins: adrenochrome, 5,6-dihydroxytryptamine, 5,7-dihydroxytryptamine, 6-hydroxydopamine and 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline.

Oral administration of heptylphysostigmine in healthy volunteers: a preliminary study.

Heptylphysostigmine (HP) is a reversible cholinesterase (ChE) inhibitor with greater lipophilicity and longer inhibitory action than the parent compound, physostigmine (Phy). Single (0.1-0.

Cerebrospinal fluid monoamine metabolites in boys with attention-deficit hyperactivity disorder.

Cerebrospinal fluid (CSF), plasma, and urinary monoamine metabolites were determined for 29 boys, aged 6-12, with attention-deficit hyperactivity disorder (ADHD). Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), the metabolites of serotonin, dopamine, and norepinephrine, respectively, correlated significantly with behavioral measures of aggression and impulsivity/hyperactivity. However, these correlations were in the unexpected direction; for example, CSF 5-HIAA correlated positively with the Brown-Goodwin Lifetime History of Aggression Scale.

In vivo evidence that nonneuronal beta-adrenoceptors as well as dopamine receptors contribute to cyclic AMP efflux in rat striatum.

We applied in vivo microdialysis to assess the effects of dopaminergic and beta-adrenergic receptor stimulation on cyclic AMP efflux in rat striatum under chloral hydrate anesthesia. Dopamine (up to 1 mM) infused for 20 min through the probe did not increase cyclic AMP, whereas both the selective dopamine D1 agonist SKF 38393 and D2 antagonist sulpiride produced modest increases. It is interesting that the beta-adrenoceptor agonist isoproterenol produced a marked increase (204.

Localization of neurokinin A and chromogranin A immunoreactivity in the developing porcine adrenal medulla.

The presence of neurokinin A immunoreactivity was studied in the chromaffin cells of the porcine adrenal medulla and in the nerve fibres innervating the adrenal gland during ontogenic development. For comparison, chromogranin A immunoreactivity was used as a marker for chromaffin cells. Whereas chromogranin A was found in chromaffin cells through all steps in embryonic development, three developmental stages of neurokinin A immunoreactivity could be distinguished.

Catecholamines in depression: an update.

Despite extensive research, the biochemical abnormalities underlying the predisposition to and the pathogenesis of affective disorders remain to be clearly established. Efforts to study norepinephrine (NE) output and function have utilized biochemical assays, neuroendocrine challenge strategies, and measures of peripheral blood cell receptors; the cumulative database points to a dysregulation of the noradrenergic system. Depressed patients (in particular, melancholic, unipolar subjects) excrete disproportionately greater amounts of NE and its major extraneuronal metabolite, normetanephrine, than do controls.

Comparative tolerability profiles of the newer versus older antidepressants.

Although the standard tricyclic antidepressants (TCAs) are generally effective in the treatment of depression, they can cause several troublesome adverse effects. Chief among these are their anticholinergic actions, which range from annoying dryness of the mouth and constipation to potentially dangerous urinary retention and confusion or delirium in the ill and elderly. Cardiovascular effects of TCAs include orthostatic hypotension, tachycardia and cardiac conduction slowing.

Differences in the distribution of cytochrome b561 and synaptophysin in dog splenic nerve: a biochemical and immunocytochemical study.

Compared with neurons of the CNS, the organization of the peripheral adrenergic axon and nerve terminal is more complex because two types of neurotransmitter-containing vesicles, i.e., large (LDVs) and small dense-core vesicles, coexist with the axonal reticulum (AR) and the well-characterized small synaptic vesicles.

A new approach in the diagnosis and follow-up of bladder cancer. FISH analysis of urine, bladder washings, and tumors.

The aim of the present study was to ascertain whether fluorescence in situ hybridization (FISH) of urine could be a useful approach in bladder cancer. Herein, we present the cytogenetic and FISH findings in patients with and without bladder cancer. The samples examined with FISH consisted of urine, bladder washings, and tumor tissue, when available.

Ultrastructural localization of neuropeptide Y-immunoreactivity in the axonal reticulum elements, accumulating anterogradely in transected rat sciatic nerve.

The detection of dopamine-beta-hydroxylase and cytochrome B561 on the membranes of the axonal reticulum demonstrated that in sympathetic neurons the different compartments of the axonal reticulum participate in the formation of neurosecretory vesicles. In the present study we tried to reveal that the components of the vesicular content are also channeled along the axonal reticulum, by examining whether neuropeptide Y could be localized in elements of the axonal reticulum. Therefore 6 h transected rat sciatic nerve was embedded in glycolmethacrylate and an immunogold labeling was performed.

Effects of chronic lithium treatment on platelet PKC isozymes in Alzheimer's and elderly control subjects.

Patients with Alzheimer's disease (AD) have been reported to have abnormalities in peripheral cells similar to some of those found in the brain, including decreased levels of protein kinase C (PKC) in fibroblasts. Since increasing evidence suggests that lithium affects PKC function, we investigated the effects of 3 weeks of lithium administration on the immunolabeling of 4 PKC isozymes (alpha, beta, epsilon, and zeta) in particulate and soluble fractions from platelets of 7 patients with probable AD and 6 age-matched controls. AD patients had significantly less particulate or membrane-associated PKC zeta than normals during the placebo phase (P < 0.

Soluble serotonin and catecholamine binding proteins in the bovine adrenal medulla.

The soluble serotonin-binding proteins (SBP) present in the adrenal medulla and in chromaffin cells, are very similar to those reported for the bovine brain and retina. Binding of [3H]serotonin and [3H]dopamine to these SBP is increased by Fe2+ but not by Fe3+. At an optimal concentration of Fe2+ (0.

Binding of serotonin and dopamine to 'serotonin binding proteins' in bovine frontal cortex: evidence for iron-induced oxidative mechanisms.

Binding of [3H]serotonin and of [3H]dopamine to serotonin binding proteins (SBP) from soluble extracts of bovine frontal cortex is increased by Fe2+ but not by Fe3+. It was generally believed that Fe2+ first binds to sulfhydryl groups of SBP and that the monoamines form coordination bonds with the trapped iron. We report two series of findings that are incompatible with this mechanism.

Murine pharmacokinetics and antitumor efficacy of the photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a.

The combination of the new photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) and laser light of wavelength 665 nm showed antitumor activity against two s.c.-implanted murine tumors.

Pediatric cataracts.

The presentation, etiology, diagnostic examination, and management of pediatric cataracts are discussed in this article. If untreated, cataracts result in significant visual deprivation. Evaluation of the pupillary light reflex should become an integral part of every pediatrician's physical examination.

Idazoxan, an alpha 2 antagonist, augments fluphenazine in schizophrenic patients: a pilot study.

Idazoxan, a selective alpha 2-adrenergic antagonist, was added to stable doses of fluphenazine treatment in six patients with schizophrenia who participated in a double-blind, placebo-controlled pharmacologic study. Compared with fluphenazine alone, combining idazoxan (mean dose, 120 mg/day) with fluphenazine (mean dose, 28 mg/day) resulted in a significant decrease in Brief Psychiatric Rating Scale total symptoms (p < 0.05).