Possible precipitants of psychiatric hospitalization in patients with major depression: results from the Jerusalem Collaborative Depression Project.

In spite of substantial advances in the treatment of major depression by pharmacotherapy and other means, a significant number of depressed patients require hospitalization. In the context of the Jerusalem Collaborative Depression Project, possible precipitants of psychiatric hospitalization were sought in a cohort of patients (n = 107) who were admitted to hospitals in the Jerusalem area during a 14-month period because of a depressive episode. The patients fulfilled DSM III-R criteria for major depression, single or recurrent; bipolar 1 disorder, depressed or mixed; bipolar 2, depressed. The cohort encompassed more than two thirds of potential subjects admitted during this period with the ICD-9 equivalents of the specified diagnoses (as reported to the Israel Ministry of Health National Psychiatric Case Register) and were similar to the entire potential population in terms of their diagnostic breakdown. The patients underwent extensive socio-demographic and clinical evaluation that included detailed documentation of treatment received prior to hospitalization. Notwithstanding the absence of a comparison group of depressed patients who were not hospitalized, a number of potential precipitants were identified. These included older age (55.2% > 60 years, 20.6% > 70 years), immigration to Israel during the preceding 5 years (34.7%), concomitant physical illness (60%) which was associated with moderate to severe disability in 41% and poor quality of antidepressant pharmacotherapy prior to hospitalisation (only 24.3% received an adequate trial of antidepressant medication). Further evaluation of these and other potential factors could facilitate targeting of patient groups at particular risk for hospitalization and reduce the need for it.     

Dose-dependent effect of cholinotoxin AF64A on the cholinergic elements of the cingulum bundle in rat

Previous studies revealed that cholinergic neurons possessing long axons are extremely sensitive to ethylcholine aziridinium ion (AF64A) administration [Neuropharmacology 31 (1992) 397]. In the present paper we examined the effect of AF64A on the cholinergic elements of the cingulum bundle. Seven days after AF64A administration choline acetyltransferase (ChAT)-immunoreactive fibers were extensively damaged on the dorsal part of cingulum bundle. These findings are the first reporting damage by AF64A to this brain region.     

Lipocalin type prostaglandin D-synthase: which role in male fertility?

Lipocalin type prostaglandin-D-synthase (L-PGDS), also called beta-trace, is an extracellular protein very abundant in compartments beyond blood-tissue barriers, such as the cerebrospinal fluid, the aqueous humor, the amniotic fluid and the seminal fluid. In the latter fluid the major function of L-PGDS does not seem to be the synthesis of prostaglandin D(2) (PGD(2)) from its precursor PGH(2), which is very unstable in aqueous solution. Instead, seminal L-PGDS, an important carrier of bile pigments, retinoids, thyroid hormones and essential fatty acids, would contribute to providing, beyond the blood-testis barrier, thyroid hormones and retinoids to the developing germ cells in the seminiferous tubules and the maturing spermatozoa in the epididymis.     

Electroconvulsive Therapy in Mania: Successful Outcome Despite Short Duration of Convulsions

A duration of 25-30 s of convulsions in electroconvulsive therapy (ECT) is thought to be the minimum necessary for an adequate treatment. We describe three manic attacks in a 48-year-old patient resistant to psychotropic drugs who responded to successive courses of ECT, each with unusually short durations of seizures.     

In vitro and in vivo demonstration of physically and chemically in situ gelling NIPAAm-based copolymer system

Poly(NIPAAm-co-hydroxyethylmethacarylate (HEMA)) acrylate and poly(NIPAAm-co-cysteine ethyl ester (CysOEt)) were synthesized and characterized by GPC(gel permeation chromatography), rheology, NMR (nuclear magnetic resonance), and Ellman’s method. Upon mixing of these materials in aqueous solution, they formed gels immediately at body temperature owing to temperature-driven physical gelling, and gradually cured by chemical cross-linking through Michael-type addition reactions between thiols and acrylates. The rate of nucleophilic attack in the Michael-type addition reaction was shown to be highly dependent on the mole ratio of thiol to acrylate at neutral pH. Physical and chemical gelation improved the mechanical properties of the materials compared to purely physical gels. In vitro and in vivo results revealed that chemical and physical gels formed stiffer less viscoelastic materials compared to purely physical gels. Physical and chemical gel systems using thermosensitive polymer with acrylates and thermosensitive polymer with thiols showed minimum toxicity.     

Intracerebroventricular administration of ethylcholine mustard aziridinium ion (AF64A) reduces release of acetylcholine from rat hippocampal slices

Ethylcholine mustard aziridinium ion (AF64A), or vehicle, was infused bilaterally (3 nmol/3 microliter per side) into the lateral ventricles of rats. The effect of such treatment on various cholinergic responses was measured in the hippocampus, cortex and striatum. Potassium-stimulated release of acetylcholine from superfused slices of hippocampus was reduced, 7 and 21 days after treatment with AF64A, to 24 and 35% of control, respectively. The activity of choline acetyltransferase in the hippocampus also decreased, to 42% of control, both 7 and 21 days after treatment with AF64A. Similarly, the activity of acetylcholinesterase and the high affinity transport of choline in the hippocampus were reduced, to 40 and 30% of control; and to 33 and 48% of control, respectively, 7 and 21 days after treatment with AF64A. Synthesis of acetylcholine in slices of hippocampus was also decreased after treatment with AF64A (71 and 51% of control, 7 and 21 days post-AF64A respectively). Only the binding of [3H]QNB in the hippocampus was unchanged at 7 days after treatment with AF64A, although a small reduction (11%) was noted 21 days after treatment with AF64A. The activity of choline acetyltransferase and acetylcholinesterase, the high-affinity transport of choline and the binding of [3H]QNB in cortex and striatum were unaffected by treatment with AF64A under the same experimental conditions. Using a substantially smaller dose than that earlier reported in mice, the earlier finding was thus confirmed, and extended, in rats, of a highly selective effect of AF64A on several components of the cholinergic system. Under the conditions of this study, these effects appeared to be confined to the hippocampus.     

Transmembrane distribution of lithium and sodium in erythrocytes of depressed patients

In this investigation the intracellular: extracellular distribution of lithium across the erythrocyte membrane (RBC lithium distribution) was studied in vitro and in vivo. The in vitro studies were conducted by incubating cells from drug-free subjects in lithium-containing physiologic media. The in vivo studies consisted of measurements of plasma and erythrocyte (RBC) lithium and sodium concentrations during lithium carbonate treatment. Previous observations of a correlation between in vitro and in vivo RBC lithium distribution values were verified, and it was found that addition of 0.1 mM ouabain to the in vitro incubation media abolished this correlation. To examine the relationship between RBC lithium distribution and specific clinical features of depression, in vitro studies were conducted with RBCs from 20 depressed patients and 14 nondepressed control subjects. The patients were categorized as having bipolar (manic-depressive), unipolar, or secondary depressive disorders. After in vitro incubation with lithium for 48 h, the RBCs from bipolar patients had lithium distribution values that were similar to those observed in ouabain-treated cells. It appears that the lithium transport characteristics of RBCs of bipolar patients may differ from those of other depressed patients or nondepressed subjects.     

Effects of amitriptyline and imipramine on brain amine neurotransmitter metabolites in cerebrospinal fluid

The effects of amitriptyline (AMI) or imipramine (IMI) on levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) (the major brain metabolites of the neurotransmitters norepinephrine [NE], serotonin [5-HT], and dopamine [DA]) in cerebrospinal fluid were determined in 66 subjects with unipolar and bipolar depression. There were significant reductions in MHPG and 5-HIAA levels for the depressed group taken as a whole, but levels of HVA did not change significantly. The changes were similar when subjects were grouped as treated with AMI and IMI and with unipolar and bipolar depression. Reductions in MHPG and 5-HIAA levels were greater in women than in men. In all subjects with depression and in those treated with AMI and IMI, amine metabolite changes did not differ significantly between those who had a positive clinical response to drug therapy and those who did not. Responders with bipolar depression had smaller reductions in MHPG levels than did responders with unipolar depression. The similar effects of AMI and IMI on MHPG and 5-HIAA differ from the dissimilar effects of the two drugs on NE and 5-HT amine uptake systems reported in animal and in in vitro studies. Results provide conclusive evidence of the effects of AMI and IMI on noradrenergic and serotonergic (but not dopaminergic) systems in patients with depression.