Development of a fully coupled diabatic spin-orbit model for the photodissociation of phenyl iodide.

The theoretical treatment of the quantum dynamics of the phenyl iodide photodissociation requires an accurate analytical potential energy surface (PES) model. This model must also account for spin-orbit (SO) coupling. This study is the first step to construct accurate SO coupled PESs, namely, for the C-I dissociation coordinate.

A long-term moderate magnesium-deficient diet aggravates cardiovascular risks associated with aging and increases mortality in rats.

Objective: The present study aimed to show whether long-term moderate magnesium (Mg)-deficient (150 mg/kg) and Mg-supplemented (3200 mg/kg) diets (versus control diet: 800 mg/kg), modified the occurrence of cardiovascular risk induced by aging in the rat.

Methods: Cardiovascular and arterial functions were determined by a systemic hemodynamic study and by ex vivo measurements of vasoconstriction and endothelium dependent-vasorelaxation. Arterial wall structure was determined using pressure myograph chamber and histomorphometric methods.

Variations of dopamine, serotonin, and amino acid concentrations in Noda epileptic rat (NER) retina.

Noda epileptic rats (NER) exhibit frequent spontaneous tonic-clonic convulsions which represent a valuable model of human epilepsy. If implication of brain neurotransmitters was largely reported, little is known about retina. However, it has been reported that human epilepsy syndrome varies not only with the location of seizure foci but also according to rhythmic patterns, for which retina has a major role in the transmission of external light-dark cycle information.

Serotonin synthesis and its light-dark variation in the rat retina.

Retinal circadian rhythms are driven by an intrinsic oscillator, using chemical signals such as melatonin, secreted by photoreceptor cells. The purpose of the present work was to identify the origin of serotonin, the precursor of melatonin, in the retina of adult rat, where no immunoreactivity for serotonin or tryptophan hydroxylase had ever been detected. To demonstrate local synthesis of serotonin in the rat retina, substrates of tryptophan hydroxylase, the first limiting enzyme in the serotonin pathway, have been used.

Evidence from a population pharmacokinetics analysis for a major effect of CYP1A2 activity on inter- and intraindividual variations of clozapine clearance.

Interindividual variations of clozapine clearance could be related to individual CYP1A2 activity. A population approach was used to investigate clozapine pharmacokinetics of multiple doses of clozapine in patients. Clozapine plasma concentrations were obtained in 23 patients from therapeutic drug monitoring (83 samples).

Retinal TUNEL-positive cells and high glutamate levels in vitreous humor of mutant quail with a glaucoma-like disorder.

Purpose: To investigate whether retinal cell death observed in an avian glaucoma-like disorder occurs by apoptosis and whether an increase in excitotoxic amino acid concentration in the vitreous humor is associated temporally with cell death in the retina.

Methods: Presumptive retinal apoptotic nuclei were identified by histochemical detection of DNA fragmentation (by TdT-dUTP terminal nick-end labeling [TUNEL]), and vitreal concentrations of glutamate and several other amino acids were determined by high-pressure liquid chromatography with fluorometric detection in the al mutant quail (Coturnix coturnix japonica) in which a glaucoma-like disorder develops spontaneously.

Results: TUNEL-labeled nuclei were located mostly in the ganglion cell layer (GCL) in the retina of mutant quails 3 months after hatching.

Day and night dysfunction in intraretinal melatonin and related indoleamines metabolism, correlated with the development of glaucoma-like disorder in an avian model.

As previous studies have suggested that melatonin and serotonin may be involved in the regulation of intraocular pressure, retinal concentrations of melatonin, 5-HT, and related indoleamines measured at day and at night were studied during the development of a glaucoma-like disorder with increased intraocular pressure in the al mutant quail. Indoleamine levels were determined by HPLC with electrochemical detection in 1-month-, 3-month-, and 7-month-old al mutant and control quails. Morphology and numbers of melatonin-synthesizing and 5-HT-containing cells, labelled immunohistochemically with an anti-hydroxyindol-0-methyltransferase (HIOMT) antibody and an anti-5-HT antibody, respectively, were studied.

Determination of melatonin in rat pineal, plasma and retina by high-performance liquid chromatography with electrochemical detection.

A sensitive method for the routine measurement of endogenous melatonin (MEL) in pineal, retina and plasma rat tissues has been developed using reversed-phase high-performance liquid chromatography with electrochemical detection. Quantification limit for MEL was 0.2 ng/mg protein in pineal, 15 pg/ml in plasma and 2.

Dopamine inhibits melatonin synthesis in photoreceptor cells through a D2-like receptor subtype in the rat retina: biochemical and histochemical evidence.

An intrinsic oscillator, using dopamine and melatonin as antagonist signals, controls rhythmic events in the retina of nonmammals. The purpose of the present work was to localize and characterize a dopamine receptor responsible for the nocturnal inhibition of melatonin synthesis in photoreceptor cells in a mammalian retina. An antibody against the D2 receptor stained photoreceptor cell inner segments of the rat retina.

Changes in retinal dopaminergic cells and dopamine rhythmic metabolism during the development of a glaucoma-like disorder in quails.

Purpose: To examine the possible correlation between a dysfunction of the daily rhythm of retinal dopamine (DA) and the development of a glaucoma-like disorder in an animal model, the al mutant quail (Coturnix coturnix japonica).

Methods: The morphology and density of DA-containing cells labeled immunohistochemically with an anti-tyrosine hydroxylase (TH) antibody were correlated with the diurnal and nocturnal contents of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) determined by high-pressure liquid chromatography with electrochemical detection.

Results: The number of TH-immunoreactive cells was lower than normal in mutant quails suffering from the disorder.

Structure-activity relationships for substrates and inhibitors of pineal 5-hydroxytryptamine-N-acetyltransferase: preliminary studies.

Tryptamine, (1-naphthyl)ethylamine and phenethylamine derivatives were tested as substrates of ovine pineal serotonin-N-acetyl transferase (5-HT-NAT), a key enzyme involved in the synthesis of melatonin. Almost all of the indole derivatives possessed affinity similar to that of tryptamine (Km = 0.05 mM), while the substituted naphthalene and phenyl derivatives were less potent.

Changes in dopamine metabolism in rat forebrain regions after cessation of long-term fluoxetine treatment: relationship with brain concentrations of fluoxetine and norfluoxetine.

We examined the effects of repeated administration of the selective serotonin uptake inhibitor (SSRI) fluoxetine (Flx) (5, 10, or 15 mg/kg i.p., twice daily for 21 days) on brain and plasma concentrations of the parent drug and its active desmethyl metabolite, norfluoxetine (NFlx), in rats during the 21-day regimen as well as after cessation of drug treatment.

6-Fluoro-serotonin as a substrate for the neuronal serotonin transporter.

6-Fluoro-serotonin (6F-5-HT) was previously identified in the rat brain after peripheral administration of 6-fluoro-DL-tryptophan, a serotonin (5-HT) synthesis inhibitor. These present studies, performed with rat brain synaptosomes show that: i-neuronal 6F-5-HT uptake partly involved the 5-HT transporter since it was inhibited by clomipramine, a 5-HT uptake inhibitor, ii-6F-5-HT blocked the synaptosomal uptake of 3H-5-HT, with an IC50 value of 98 +/- 13 nM, and iii- 6F-5-HT induced 3H-5-HT release from preloaded synaptosomes, with an EC50 value of 95 +/- 6 nM; this release was decreased in the presence of clomipramine, suggesting the involvement of the 5-HT transporter. This release was also reduced when using synaptosomes from reserpinized rats, suggesting that the vesicular pool also participates to the 3H-5-HT release induced by 6F-5-HT.

Metabolism of 6-fluoro-DL-tryptophan and its specific effects on the rat brain serotoninergic pathway.

We administered 6-fluoro-DL-tryptophan (6F-Trp) to rats (50-200 mg/kg i.p.) and evaluated its neurochemical effects on central catechole and indole compounds; we also determined the time course of its action, together with its metabolism and kinetics in four rat brain areas.

Dopaminergic interplexiform cells in the retina of pigmented and hypopigmented quails (Coturnix coturnix japonica).

Interplexiform cells (IPCs) have not been previously described as a component of the population of tyrosine hydroxylase (TH) immunoreactive (presumably dopaminergic) cells in the avian retina. In this study, carried out in both pigmented and imperfect albino mutant quails (Coturnix coturnix japonica), we initially describe TH immunoreactive cells in the inner nuclear layer whose internal dendritic arborization extends into strata 1, 3 and 4/5 of the inner plexiform layer. Then, we describe ascending processes arising from the somata or proximal dendrites of these cells.

Time course of brain serotonin metabolism after cessation of long-term fluoxetine treatment in the rat.

The effects of repeated fluoxetine (Flx) administration (5, 10, or 15 mg/kg i.p., twice daily for 21 days) on serotonin and 5-HIAA metabolism were examined in the hypothalamus, hippocampus, pons medulla and cerebral cortex of rats killed 1-28 days after the last dose.

Albumin binding and brain uptake of 6-fluoro-DL-tryptophan: competition with L-tryptophan.

We investigated potential competition between L-tryptophan (TRP) and 6-fluoro-DL-tryptophan (6-F-TRP) for binding to albumin and for passage through the blood-brain barrier (BBB). In experiments based on equilibrium dialysis, albumin (600 microM) bound about 80% of TRP and 50% of 6-F-TRP with affinity constants (Ka) of 3.7 +/- 0.

In vivo evidence for carrier-mediated brain uptake of a new 2-amino-2-oxazoline (COR3224) via the purine transport system in rat.

We studied the brain uptake of a new 2-amino-2-oxazolamines derivative (COR3224) in the rat by means of the rapid intracarotid injection technique described by Oldendorf. The brain uptake index (BUI) of labelled COR3224 decreased progressively from 10% to 5% when concentrations of unlabelled compound were increased. The effect of various compounds indicated that COR3224 is transported into the brain by the purine carrier.